首页 > 最新文献

Neurobiology of Stress最新文献

英文 中文
Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects 主观压力与酒精治疗期间的任何饮酒行为:消除人内和人与人之间的自回归效应
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-16 DOI: 10.1016/j.ynstr.2023.100602
Katie Witkiewitz , Christian C. Garcia , Bengt O. Muthén

Alcohol use has been shown to increase stress, and there is some evidence that stress predicts subsequent alcohol use during treatment for alcohol use disorder (AUD), particularly among females who are more likely to report coping-motivated drinking. Gaining a better understanding of the processes by which stress and alcohol use are linked during treatment could potentially inform AUD treatment planning. The current study aimed to characterize the association between stress and drinking during the course of AUD treatment and whether there were sex differences in these associations. Secondary data analyses of the COMBINE study (N = 1375; 69% male, 76.3% non-Hispanic and white, average age of 44.4 years) were conducted to examine self-reported perceived stress and alcohol consumption across 16 weeks of treatment for AUD using a Bayesian random-intercept cross-lagged panel model. There was stronger evidence for any alcohol use predicting greater than typical stress in subsequent weeks and less strong evidence for stress increasing the subsequent probability of alcohol use, particularly among males. For females, greater stress predicted subsequent drinking earlier in the treatment period, and a lower probability of subsequent drinking in the last week of treatment. Interventions might specifically focus on targeting reductions in stress following drinking occasions.

酒精使用已被证明会增加压力,而且有证据表明,在酒精使用障碍(AUD)的治疗过程中,压力会预示随后的酒精使用,尤其是在女性中,她们更有可能报告出于应对动机的饮酒。更好地了解治疗过程中压力与饮酒之间的关联过程,有可能为酒精使用障碍的治疗规划提供参考。本研究旨在描述 AUD 治疗过程中压力与饮酒之间的关系,以及这种关系是否存在性别差异。本研究对 COMBINE 研究(N = 1375;69% 为男性,76.3% 为非西班牙裔和白人,平均年龄为 44.4 岁)进行了二次数据分析,采用贝叶斯随机截距交叉滞后面板模型研究了 AUD 治疗的 16 周期间自我报告的感知压力和饮酒量。有更有力的证据表明,任何饮酒行为都预示着随后几周的压力会大于典型压力,而压力增加随后饮酒概率的证据则不那么有力,尤其是在男性中。对于女性来说,更大的压力预示着在治疗期间更早地饮酒,而在治疗的最后一周饮酒的概率更低。干预措施可特别侧重于减少饮酒后的压力。
{"title":"Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects","authors":"Katie Witkiewitz ,&nbsp;Christian C. Garcia ,&nbsp;Bengt O. Muthén","doi":"10.1016/j.ynstr.2023.100602","DOIUrl":"10.1016/j.ynstr.2023.100602","url":null,"abstract":"<div><p>Alcohol use has been shown to increase stress, and there is some evidence that stress predicts subsequent alcohol use during treatment for alcohol use disorder (AUD), particularly among females who are more likely to report coping-motivated drinking. Gaining a better understanding of the processes by which stress and alcohol use are linked during treatment could potentially inform AUD treatment planning. The current study aimed to characterize the association between stress and drinking during the course of AUD treatment and whether there were sex differences in these associations. Secondary data analyses of the COMBINE study (N = 1375; 69% male, 76.3% non-Hispanic and white, average age of 44.4 years) were conducted to examine self-reported perceived stress and alcohol consumption across 16 weeks of treatment for AUD using a Bayesian random-intercept cross-lagged panel model. There was stronger evidence for any alcohol use predicting greater than typical stress in subsequent weeks and less strong evidence for stress increasing the subsequent probability of alcohol use, particularly among males. For females, greater stress predicted subsequent drinking earlier in the treatment period, and a lower probability of subsequent drinking in the last week of treatment. Interventions might specifically focus on targeting reductions in stress following drinking occasions.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000905/pdfft?md5=698995a43eb50ac178a15690581285e1&pid=1-s2.0-S2352289523000905-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138741925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Theta oscillatory dynamics serving cognitive control index psychosocial distress in youth 为认知控制提供服务的 Theta 振荡动态指标:青少年的社会心理困扰
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-15 DOI: 10.1016/j.ynstr.2023.100599
Mikki Schantell , Brittany K. Taylor , Amirsalar Mansouri , Yasra Arif , Anna T. Coutant , Danielle L. Rice , Yu-Ping Wang , Vince D. Calhoun , Julia M. Stephen , Tony W. Wilson

Background

Psychosocial distress among youth is a major public health issue characterized by disruptions in cognitive control processing. Using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, we quantified multidimensional neural oscillatory markers of psychosocial distress serving cognitive control in youth.

Methods

The sample consisted of 39 peri-adolescent participants who completed the NIH Toolbox Emotion Battery (NIHTB-EB) and the Eriksen flanker task during magnetoencephalography (MEG). A psychosocial distress index was computed with exploratory factor analysis using assessments from the NIHTB-EB. MEG data were analyzed in the time-frequency domain and peak voxels from oscillatory maps depicting the neural cognitive interference effect were extracted for voxel time series analyses to identify spontaneous and oscillatory aberrations in dynamics serving cognitive control as a function of psychosocial distress. Further, we quantified the relationship between psychosocial distress and dynamic functional connectivity between regions supporting cognitive control.

Results

The continuous psychosocial distress index was strongly associated with validated measures of pediatric psychopathology. Theta-band neural cognitive interference was identified in the left dorsolateral prefrontal cortex (dlPFC) and middle cingulate cortex (MCC). Time series analyses of these regions indicated that greater psychosocial distress was associated with elevated spontaneous activity in both the dlPFC and MCC and blunted theta oscillations in the MCC. Finally, we found that stronger phase coherence between the dlPFC and MCC was associated with greater psychosocial distress.

Conclusions

Greater psychosocial distress was marked by alterations in spontaneous and oscillatory theta activity serving cognitive control, along with hyperconnectivity between the dlPFC and MCC.

背景青少年的心理社会困扰是一个重大的公共卫生问题,其特点是认知控制处理过程受到干扰。我们利用美国国家心理健康研究所的研究领域标准(RDoC)框架,量化了青少年认知控制过程中心理社会困扰的多维神经振荡标记。方法样本由 39 名青少年组成,他们在脑磁图(MEG)检查中完成了美国国家心理健康研究所工具箱情绪测试(NIHTB-EB)和埃里克森侧翼任务。通过对 NIHTB-EB 的评估结果进行探索性因子分析,计算出了社会心理压力指数。我们对脑磁图数据进行了时频域分析,并从描绘神经认知干扰效应的振荡图中提取峰值体素进行体素时间序列分析,以确定认知控制动态中的自发和振荡畸变与社会心理压力的关系。此外,我们还量化了社会心理压力与支持认知控制的区域之间的动态功能连接之间的关系。在左侧背外侧前额叶皮层 (dlPFC) 和中扣带回皮层 (MCC) 发现了 Theta 波段神经认知干扰。对这些区域的时间序列分析表明,较大的社会心理压力与前额叶皮层(dlPFC)和扣带回皮层(MCC)的自发活动升高以及扣带回皮层(MCC)的θ振荡减弱有关。最后,我们发现,dlPFC 和 MCC 之间更强的相位一致性与更严重的心理社会困扰有关。结论更严重的心理社会困扰表现为认知控制的自发和振荡θ活动的改变,以及 dlPFC 和 MCC 之间的超连接性。
{"title":"Theta oscillatory dynamics serving cognitive control index psychosocial distress in youth","authors":"Mikki Schantell ,&nbsp;Brittany K. Taylor ,&nbsp;Amirsalar Mansouri ,&nbsp;Yasra Arif ,&nbsp;Anna T. Coutant ,&nbsp;Danielle L. Rice ,&nbsp;Yu-Ping Wang ,&nbsp;Vince D. Calhoun ,&nbsp;Julia M. Stephen ,&nbsp;Tony W. Wilson","doi":"10.1016/j.ynstr.2023.100599","DOIUrl":"10.1016/j.ynstr.2023.100599","url":null,"abstract":"<div><h3>Background</h3><p>Psychosocial distress among youth is a major public health issue characterized by disruptions in cognitive control processing. Using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, we quantified multidimensional neural oscillatory markers of psychosocial distress serving cognitive control in youth.</p></div><div><h3>Methods</h3><p>The sample consisted of 39 peri-adolescent participants who completed the NIH Toolbox Emotion Battery (NIHTB-EB) and the Eriksen flanker task during magnetoencephalography (MEG). A psychosocial distress index was computed with exploratory factor analysis using assessments from the NIHTB-EB. MEG data were analyzed in the time-frequency domain and peak voxels from oscillatory maps depicting the neural cognitive interference effect were extracted for voxel time series analyses to identify spontaneous and oscillatory aberrations in dynamics serving cognitive control as a function of psychosocial distress. Further, we quantified the relationship between psychosocial distress and dynamic functional connectivity between regions supporting cognitive control.</p></div><div><h3>Results</h3><p>The continuous psychosocial distress index was strongly associated with validated measures of pediatric psychopathology. Theta-band neural cognitive interference was identified in the left dorsolateral prefrontal cortex (dlPFC) and middle cingulate cortex (MCC). Time series analyses of these regions indicated that greater psychosocial distress was associated with elevated spontaneous activity in both the dlPFC and MCC and blunted theta oscillations in the MCC. Finally, we found that stronger phase coherence between the dlPFC and MCC was associated with greater psychosocial distress.</p></div><div><h3>Conclusions</h3><p>Greater psychosocial distress was marked by alterations in spontaneous and oscillatory theta activity serving cognitive control, along with hyperconnectivity between the dlPFC and MCC.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000875/pdfft?md5=9c4c77424401dc2b21cc10cc6a1ea270&pid=1-s2.0-S2352289523000875-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blue light at night produces stress-evoked heightened aggression by enhancing brain-derived neurotrophic factor in the basolateral amygdala 夜间蓝光通过增强杏仁核基底外侧的脑源性神经营养因子,产生应激诱发的攻击性增强现象
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-15 DOI: 10.1016/j.ynstr.2023.100600
Zhenlong Li , Chau-Shoun Lee , Si Chen , Benyu He , Xinya Chen , Hsien-Yu Peng , Tzer-Bin Lin , Ming-Chun Hsieh , Cheng-Yuan Lai , Dylan Chou

Light is an underappreciated mood manipulator. People are often exposed to electronic equipment, which results in nocturnal blue light exposure in modern society. Light pollution drastically shortens the night phase of the circadian rhythm. Preclinical and clinical studies have reported that nocturnal light exposure can influence mood, such as depressive-like phenotypes. However, the effects of blue light at night (BLAN) on other moods and how it alters mood remain unclear. Here, we explored the impact of BLAN on stress-provoked aggression in male Sprague‒Dawley rats, focusing on its influence on basolateral amygdala (BLA) activity. Resident-intruder tests, extracellular electrophysiological recordings, and enzyme-linked immunosorbent assays were performed. The results indicated that BLAN produces stress-induced heightened aggressive and anxiety-like phenotypes. Moreover, BLAN not only potentiates long-term potentiation and long-term depression in the BLA but also results in stress-induced elevation of brain-derived neurotrophic factor (BDNF), mature BDNF, and phosphorylation of tyrosine receptor kinase B expression in the BLA. Intra-BLA microinfusion of BDNF RNAi, BDNF neutralizing antibody, K252a, and rapamycin blocked stress-induced heightened aggressive behavior in BLAN rats. In addition, intra-BLA application of BDNF and 7,8-DHF caused stress-induced heightened aggressive behavior in naïve rats. Collectively, these results suggest that BLAN results in stress-evoked heightened aggressive phenotypes, which may work by enhancing BLA BDNF signaling and synaptic plasticity. This study reveals that nocturnal blue light exposure may have an impact on stress-provoked aggression. Moreover, this study provides novel insights into the BLA BDNF-dependent mechanism underlying the impact of the BLAN on mood.

光线是一种不被重视的情绪调节器。现代社会中,人们经常接触电子设备,导致夜间蓝光照射。光污染大大缩短了昼夜节律的夜间阶段。临床前和临床研究报告称,夜间光照射会影响情绪,如抑郁样表型。然而,夜间蓝光(BLAN)对其他情绪的影响及其如何改变情绪仍不清楚。在这里,我们探讨了夜间蓝光对应激诱发的雄性 Sprague-Dawley 大鼠攻击行为的影响,重点是其对杏仁基底外侧(BLA)活动的影响。研究人员进行了驻留诱入试验、细胞外电生理记录和酶联免疫吸附试验。结果表明,BLAN能产生应激诱导的攻击性增强和焦虑样表型。此外,BLAN不仅能增强BLA的长期电位和长期抑制,还能导致应激诱导的BLA脑源性神经营养因子(BDNF)、成熟BDNF和酪氨酸受体激酶B磷酸化表达的升高。在BLA内微量注入BDNF RNAi、BDNF中和抗体K252a和雷帕霉素可阻止应激诱导的BLAN大鼠攻击性行为的增加。此外,在BLA内应用BDNF和7,8-DHF会导致应激诱导的天真大鼠攻击行为增强。总之,这些结果表明,BLAN 会导致应激诱发的攻击性表型增强,这可能是通过增强 BLA BDNF 信号传导和突触可塑性实现的。这项研究揭示了夜间蓝光照射可能会对应激诱发的攻击行为产生影响。此外,这项研究还为蓝光照射对情绪的影响所依赖的BLA BDNF机制提供了新的见解。
{"title":"Blue light at night produces stress-evoked heightened aggression by enhancing brain-derived neurotrophic factor in the basolateral amygdala","authors":"Zhenlong Li ,&nbsp;Chau-Shoun Lee ,&nbsp;Si Chen ,&nbsp;Benyu He ,&nbsp;Xinya Chen ,&nbsp;Hsien-Yu Peng ,&nbsp;Tzer-Bin Lin ,&nbsp;Ming-Chun Hsieh ,&nbsp;Cheng-Yuan Lai ,&nbsp;Dylan Chou","doi":"10.1016/j.ynstr.2023.100600","DOIUrl":"https://doi.org/10.1016/j.ynstr.2023.100600","url":null,"abstract":"<div><p>Light is an underappreciated mood manipulator. People are often exposed to electronic equipment, which results in nocturnal blue light exposure in modern society. Light pollution drastically shortens the night phase of the circadian rhythm. Preclinical and clinical studies have reported that nocturnal light exposure can influence mood, such as depressive-like phenotypes. However, the effects of blue light at night (BLAN) on other moods and how it alters mood remain unclear. Here, we explored the impact of BLAN on stress-provoked aggression in male Sprague‒Dawley rats, focusing on its influence on basolateral amygdala (BLA) activity. Resident-intruder tests, extracellular electrophysiological recordings, and enzyme-linked immunosorbent assays were performed. The results indicated that BLAN produces stress-induced heightened aggressive and anxiety-like phenotypes. Moreover, BLAN not only potentiates long-term potentiation and long-term depression in the BLA but also results in stress-induced elevation of brain-derived neurotrophic factor (BDNF), mature BDNF, and phosphorylation of tyrosine receptor kinase B expression in the BLA. Intra-BLA microinfusion of BDNF RNAi, BDNF neutralizing antibody, K252a, and rapamycin blocked stress-induced heightened aggressive behavior in BLAN rats. In addition, intra-BLA application of BDNF and 7,8-DHF caused stress-induced heightened aggressive behavior in naïve rats. Collectively, these results suggest that BLAN results in stress-evoked heightened aggressive phenotypes, which may work by enhancing BLA BDNF signaling and synaptic plasticity. This study reveals that nocturnal blue light exposure may have an impact on stress-provoked aggression. Moreover, this study provides novel insights into the BLA BDNF-dependent mechanism underlying the impact of the BLAN on mood.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000887/pdfft?md5=3bc75819bd5857805476508414409697&pid=1-s2.0-S2352289523000887-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138713250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats 早期社会隔离对雌雄马氏撒丁岛酒精偏好大鼠的糖皮质激素受体系统和觅酒行为产生不同影响
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-07 DOI: 10.1016/j.ynstr.2023.100598
F. Benvenuti , S. De Carlo , L. Rullo , L. Caffino , L.M. Losapio , C. Morosini , M. Ubaldi , L. Soverchia , N. Cannella , E. Domi , S. Candeletti , F. Mottarlini , L. Fattore , P. Romualdi , F. Fumagalli , V. Trezza , M. Roberto , R. Ciccocioppo

Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of Nr3c1 mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.

出生后发育过程中的不良早期生活经历会诱发应激系统发生长期的神经生物学变化,从而影响随后的行为,包括罹患酒精使用障碍的倾向。在此,我们将经过基因筛选的雌雄马氏撒丁岛酒精偏好大鼠(msP)和Wistar大鼠暴露于从出生后第14天(PND14)到PND21的轻度、反复的社会剥夺中,并研究了早期社会隔离(ESI)对糖皮质激素受体(GR)系统以及对成年后饮酒和酗酒倾向的影响。我们发现,ESI会导致雄性msP大鼠前额叶皮层(PFC)的GR基因和蛋白表达水平升高,而雌性msP大鼠则不会。在雌性 Wistars 大鼠中,ESI 导致 Nr3c1 mRNA 水平显著下调,GR 蛋白水平降低。在雄性和雌性 msP 大鼠中,PND35 的血浆皮质酮水平相似,且不受 ESI 的影响。雌性 Wistar 大鼠的皮质酮水平高于雄性,这与 ESI 无关。在酒精自我给药实验中,我们发现药理应激剂育亨宾(0.0、0.312、0.625 和 1.25 毫克/千克)会增加两个品系大鼠的酒精自我给药,与 ESI 无关。消退后,0.625 毫克/千克育亨宾可显著恢复雌性大鼠对酒精的寻求。ESI增强了雌性msP大鼠的恢复能力。总之,本研究结果表明,出生后第三周内反复的社会剥夺会影响 GR 的表达,其影响方式与品系和性别有关:这种影响可能至少部分导致了雌性 mSP 大鼠对育亨宾诱导的酒精寻求效应更加敏感。
{"title":"Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats","authors":"F. Benvenuti ,&nbsp;S. De Carlo ,&nbsp;L. Rullo ,&nbsp;L. Caffino ,&nbsp;L.M. Losapio ,&nbsp;C. Morosini ,&nbsp;M. Ubaldi ,&nbsp;L. Soverchia ,&nbsp;N. Cannella ,&nbsp;E. Domi ,&nbsp;S. Candeletti ,&nbsp;F. Mottarlini ,&nbsp;L. Fattore ,&nbsp;P. Romualdi ,&nbsp;F. Fumagalli ,&nbsp;V. Trezza ,&nbsp;M. Roberto ,&nbsp;R. Ciccocioppo","doi":"10.1016/j.ynstr.2023.100598","DOIUrl":"10.1016/j.ynstr.2023.100598","url":null,"abstract":"<div><p>Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of <em>Nr3c1</em> mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000863/pdfft?md5=2e1155c369695372c4d55e8168ed7c64&pid=1-s2.0-S2352289523000863-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138548498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prior experience with behavioral control over stress facilitates social dominance 先前的压力行为控制经验有助于社会支配
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-06 DOI: 10.1016/j.ynstr.2023.100597
Philip T. Coleman , Gabriel W. Costanza-Chavez , Heather N. Martin, Jose Amat, Matthew G. Frank, Rory J. Sanchez, Garrett J. Potter, Simone M. Mellert, Rene K. Carter, Gianni N. Bonnici, Steven F. Maier, Michael V. Baratta

Dominance status has extensive effects on physical and mental health, and an individual's relative position can be shaped by experiential factors. A variety of considerations suggest that the experience of behavioral control over stressors should produce winning in dominance tests and that winning should blunt the impact of later stressors, as does prior control. To investigate the interplay between competitive success and stressor control, we first examined the impact of stressor controllability on subsequent performance in a warm spot competition test modified for rats. Prior experience of controllable, but not physically identical uncontrollable, stress increased later effortful behavior and occupation of the warm spot. Controllable stress subjects consistently ranked higher than did uncontrollable stress subjects. Pharmacological inactivation of the prelimbic (PL) cortex during behavioral control prevented later facilitation of dominance. Next, we explored whether repeated winning experiences produced later resistance against the typical sequelae of uncontrollable stress. To establish dominance status, triads of rats were given five sessions of warm spot competition. The development of stable dominance was prevented by reversible inactivation of the PL or NMDA receptor blockade in the dorsomedial striatum. Stable winning blunted the later stress-induced increase in dorsal raphe nucleus serotonergic activity, as well as prevented uncontrollable stress-induced social avoidance. In contrast, endocrine and neuroimmune responses to uncontrollable stress were unaffected, indicating a selective impact of prior dominance. Together, these data demonstrate that instrumental control over stress promotes later dominance, but also reveal that winning experiences buffer against the neural and behavioral outcomes of future adversity.

支配地位对身心健康有广泛的影响,个体的相对地位可由经验因素塑造。各种各样的考虑表明,对压力源的行为控制的经验应该产生优势测试的胜利,并且胜利应该减弱后压力源的影响,就像先前的控制一样。为了研究竞争成功与压力源控制之间的相互作用,我们首先在一个改良的大鼠温点竞争测试中研究了压力源可控性对随后表现的影响。先前的可控经验,但不是物理上相同的不可控,压力增加了后来的努力行为和占领温暖点。可控压力组的排名始终高于不可控压力组。在行为控制期间,前边缘(PL)皮层的药理学失活阻止了后来的优势化。接下来,我们探讨了重复的胜利经历是否会产生后来对不可控制的压力的典型后遗症的抵抗力。为了建立优势地位,给三联大鼠进行5次温点竞争。背内侧纹状体中PL或NMDA受体阻断的可逆失活阻止了稳定优势的发展。稳定的胜利减弱了后期压力引起的中缝背核血清素活性的增加,并阻止了无法控制的压力引起的社会回避。相比之下,内分泌和神经免疫对不可控压力的反应不受影响,表明先前优势的选择性影响。总之,这些数据表明,对压力的工具控制促进了后来的支配地位,但也揭示了胜利的经历缓冲了未来逆境的神经和行为结果。
{"title":"Prior experience with behavioral control over stress facilitates social dominance","authors":"Philip T. Coleman ,&nbsp;Gabriel W. Costanza-Chavez ,&nbsp;Heather N. Martin,&nbsp;Jose Amat,&nbsp;Matthew G. Frank,&nbsp;Rory J. Sanchez,&nbsp;Garrett J. Potter,&nbsp;Simone M. Mellert,&nbsp;Rene K. Carter,&nbsp;Gianni N. Bonnici,&nbsp;Steven F. Maier,&nbsp;Michael V. Baratta","doi":"10.1016/j.ynstr.2023.100597","DOIUrl":"10.1016/j.ynstr.2023.100597","url":null,"abstract":"<div><p>Dominance status has extensive effects on physical and mental health, and an individual's relative position can be shaped by experiential factors. A variety of considerations suggest that the experience of behavioral control over stressors should produce winning in dominance tests and that winning should blunt the impact of later stressors, as does prior control. To investigate the interplay between competitive success and stressor control, we first examined the impact of stressor controllability on subsequent performance in a warm spot competition test modified for rats. Prior experience of controllable, but not physically identical uncontrollable, stress increased later effortful behavior and occupation of the warm spot. Controllable stress subjects consistently ranked higher than did uncontrollable stress subjects. Pharmacological inactivation of the prelimbic (PL) cortex during behavioral control prevented later facilitation of dominance. Next, we explored whether repeated winning experiences produced later resistance against the typical sequelae of uncontrollable stress. To establish dominance status, triads of rats were given five sessions of warm spot competition. The development of stable dominance was prevented by reversible inactivation of the PL or NMDA receptor blockade in the dorsomedial striatum. Stable winning blunted the later stress-induced increase in dorsal raphe nucleus serotonergic activity, as well as prevented uncontrollable stress-induced social avoidance. In contrast, endocrine and neuroimmune responses to uncontrollable stress were unaffected, indicating a selective impact of prior dominance. Together, these data demonstrate that instrumental control over stress promotes later dominance, but also reveal that winning experiences buffer against the neural and behavioral outcomes of future adversity.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000851/pdfft?md5=7474f724f83750dc266b51fd88687625&pid=1-s2.0-S2352289523000851-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138531805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucocorticoids modulate neural activity via a rapid non-genomic effect on Kv2.2 channels in the central nervous system 糖皮质激素通过对中枢神经系统Kv2.2通道的快速非基因组效应调节神经活动
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-25 DOI: 10.1016/j.ynstr.2023.100593
Yuqi Wang , Yuchen Zhang , Jiawei Hu , Chengfang Pan , Yiming Gao , Qingzhuo Liu , Wendong Xu , Lei Xue , Changlong Hu

Glucocorticoids are primary stress hormones that exert neuronal effects via both genomic and non-genomic signaling pathways. However, their rapid non-genomic effects and underlying mechanisms on neural activities remain elusive. In the present study, we investigated the rapid non-genomic effect of glucocorticoids on Kv2.2 channels in cultured HEK293 cells and acute brain slices including cortical pyramidal neurons and calyx-type synapses in the brain stem. We found that cortisol, the endogenous glucocorticoids, rapidly increased Kv2.2 currents by increasing the single-channel open probability in Kv2.2-expressing HEK293 cells through activation of the membrane-associated glucocorticoid receptor. Bovine serum albumin-conjugated dexamethasone, a membrane-impermeable agonist of the glucocorticoid receptor, could mimic the effect of cortisol on Kv2.2 channels. The cortisol-increased Kv2.2 currents were induced by activation of the extracellular signal-regulated protein kinase (ERK) 1/2 kinase, which could be inhibited by U0126, an antagonist of the ERK signaling pathway. In layer 2 cortical pyramidal neurons and the calyx of Held synapses, cortisol suppressed the action potential firing frequency during depolarization and reduced the successful rate upon high-frequency stimulation by activating Kv2.2 channels. We further examined the postsynaptic responses and found that cortisol did not affect the mEPSC and evoked EPSC, but increased the activity-dependent synaptic depression induced by a high-frequency stimulus train. In conclusion, glucocorticoids can rapidly activate Kv2.2 channels through membrane-associated glucocorticoid receptors via the ERK1/2 signaling pathway, suppress presynaptic action potential firing, and inhibit synaptic transmission and plasticity. This may be a universal mechanism of the glucocorticoid-induced non-genomic effects in the central nervous system.

糖皮质激素是主要的应激激素,通过基因组和非基因组信号通路发挥神经元作用。然而,它们对神经活动的快速非基因组效应和潜在机制仍然难以捉摸。在本研究中,我们研究了糖皮质激素对培养的HEK293细胞和包括皮质锥体神经元和脑干花萼型突触在内的急性脑切片中Kv2.2通道的快速非基因组效应。我们发现,内源性糖皮质激素皮质醇通过激活膜相关糖皮质激素受体,增加表达Kv2.2的HEK293细胞的单通道打开概率,从而迅速增加Kv2.2电流。牛血清白蛋白偶联地塞米松是一种糖皮质激素受体的膜不渗透性激动剂,可以模拟皮质醇对Kv2.2通道的作用。皮质醇增加的Kv2.2电流是通过激活细胞外信号调节蛋白激酶(ERK) 1/2激酶诱导的,该激酶可被ERK信号通路拮抗剂U0126抑制。在皮层第2层锥体神经元和Held突触的花萼中,皮质醇通过激活Kv2.2通道抑制去极化过程中的动作电位放电频率,降低高频刺激的成功率。我们进一步检查了突触后反应,发现皮质醇不影响mEPSC并诱发EPSC,但增加了高频刺激引起的活动依赖性突触抑制。综上所述,糖皮质激素可通过膜相关糖皮质激素受体通过ERK1/2信号通路快速激活Kv2.2通道,抑制突触前动作电位放电,抑制突触传递和可塑性。这可能是糖皮质激素诱导中枢神经系统非基因组效应的普遍机制。
{"title":"Glucocorticoids modulate neural activity via a rapid non-genomic effect on Kv2.2 channels in the central nervous system","authors":"Yuqi Wang ,&nbsp;Yuchen Zhang ,&nbsp;Jiawei Hu ,&nbsp;Chengfang Pan ,&nbsp;Yiming Gao ,&nbsp;Qingzhuo Liu ,&nbsp;Wendong Xu ,&nbsp;Lei Xue ,&nbsp;Changlong Hu","doi":"10.1016/j.ynstr.2023.100593","DOIUrl":"https://doi.org/10.1016/j.ynstr.2023.100593","url":null,"abstract":"<div><p>Glucocorticoids are primary stress hormones that exert neuronal effects via both genomic and non-genomic signaling pathways. However, their rapid non-genomic effects and underlying mechanisms on neural activities remain elusive. In the present study, we investigated the rapid non-genomic effect of glucocorticoids on Kv2.2 channels in cultured HEK293 cells and acute brain slices including cortical pyramidal neurons and calyx-type synapses in the brain stem. We found that cortisol, the endogenous glucocorticoids, rapidly increased Kv2.2 currents by increasing the single-channel open probability in Kv2.2-expressing HEK293 cells through activation of the membrane-associated glucocorticoid receptor. Bovine serum albumin-conjugated dexamethasone, a membrane-impermeable agonist of the glucocorticoid receptor, could mimic the effect of cortisol on Kv2.2 channels. The cortisol-increased Kv2.2 currents were induced by activation of the extracellular signal-regulated protein kinase (ERK) 1/2 kinase, which could be inhibited by U0126, an antagonist of the ERK signaling pathway. In layer 2 cortical pyramidal neurons and the calyx of Held synapses, cortisol suppressed the action potential firing frequency during depolarization and reduced the successful rate upon high-frequency stimulation by activating Kv2.2 channels. We further examined the postsynaptic responses and found that cortisol did not affect the mEPSC and evoked EPSC, but increased the activity-dependent synaptic depression induced by a high-frequency stimulus train. In conclusion, glucocorticoids can rapidly activate Kv2.2 channels through membrane-associated glucocorticoid receptors via the ERK1/2 signaling pathway, suppress presynaptic action potential firing, and inhibit synaptic transmission and plasticity. This may be a universal mechanism of the glucocorticoid-induced non-genomic effects in the central nervous system.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000814/pdfft?md5=cc4cab004d69b1a76abfbeeca7fd90be&pid=1-s2.0-S2352289523000814-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Environmental enrichment reverses stress-induced changes in the brain-gut axis to ameliorate chronic visceral and somatic hypersensitivity 环境富集逆转应激诱导的脑肠轴变化,改善慢性内脏和躯体超敏反应
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-24 DOI: 10.1016/j.ynstr.2023.100590
A. Orock , A.C. Johnson , E. Mohammadi , B. Greenwood-Van Meerveld

Introduction

Behavioral therapies, including cognitive behavioral therapy, hypnotherapy and stress management activities, have emerged as effective treatments for irritable bowel syndrome (IBS), a female predominant disorder of the brain-gut axis. IBS, affecting over 10% of the global population, typically presents with abnormal bowel habits and abdominal pain due to visceral hypersensitivity. While the mechanisms underlying how behavioral therapies treat IBS are still elusive, we had previously shown that chronic stress alters gene expression in brain regions critical for stress processing and nociception. We found that exposure to an enriched environment (EE), the rodent analogue of behavioral therapies, prior to and during the stressor was sufficient to prevent stress-induced changes in glucocorticoid receptor (GR) expression in the central nucleus of the amygdala (CeA) and hippocampus. Pre-exposure to EE also inhibited stress-induced increased colonic permeability and was able to block the induction of stress-induced visceral and somatic hypersensitivity. However, it remains unknown if EE can reverse chronic viscerosomatic hypersensitivity that persists following exposure to stress. We hypothesized that EE after chronic stress would be sufficient to reverse stress-induced changes in i) GR expression in the CeA and hippocampus, ii) ameliorate stress-induced colonic hyperpermeability and iii) restore normal visceral and somatic sensitivity in male and female rats.

Methods

Male and female rats were exposed to daily water avoidance stress (WAS). After confirming the rats had developed visceral hypersensitivity, 50% of the animals were housed in EE for 2 weeks while the other 50% remained in standard housing (SH). At the end of this period, we assessed visceral and somatic sensitivity. We also collected colon tissue to measure colonic permeability. Micro-punches of tissue from the CeA and hippocampus were isolated to measure GR expression. Control animals not exposed to WAS were kept in SH for the duration of the study (n = 8 per group).

Results

In both male and female rats, EE reversed stress-induced visceral (p < 0.001) and somatic (p < 0.01) hypersensitivity when compared to WAS animals housed in SH to levels comparable to control animals. EE exposure also reversed changes in GR expression in both the hippocampus (p < 0.01) and CeA (p < 0.01), normalizing GR expression to control levels. EE exposure ameliorated stress-induced colonic hyperpermeability in both male (p < 0.01) and female (p < 0.01) rats compared to WAS rats in SH.

Conclusion

Our findings suggest that behavioral therapies are viable therapeutic options for IBS as they can counter the stress-induced pathophysiology underlying IBS symptoms including visceral hypersensitivity, increased colonic permeability and altered gene expression.

行为疗法,包括认知行为疗法、催眠疗法和压力管理活动,已经成为肠易激综合征(IBS)的有效治疗方法,IBS是一种女性主要的脑-肠轴疾病。IBS影响全球10%以上的人口,通常表现为肠道习惯异常和内脏过敏引起的腹痛。虽然行为疗法治疗肠易激综合征的机制仍然难以捉摸,但我们之前已经表明,慢性压力会改变大脑中对压力处理和伤害感觉至关重要的区域的基因表达。我们发现,在应激源之前和期间暴露于富集环境(EE),即行为治疗的啮齿动物模拟物,足以防止应激引起的杏仁核中央核(CeA)和海马糖皮质激素受体(GR)表达的变化。预暴露于EE也抑制应激诱导的结肠通透性增加,并能够阻断应激诱导的内脏和躯体超敏反应的诱导。然而,EE是否可以逆转暴露于压力后持续存在的慢性脏器体超敏反应仍不清楚。我们假设慢性应激后的EE足以逆转应激诱导的变化:1)CeA和海马GR表达,2)改善应激诱导的结肠高通透性,3)恢复雄性和雌性大鼠正常的内脏和身体敏感性。方法将雄性和雌性大鼠置于每日避水应激(WAS)下。在确认大鼠出现内脏过敏后,50%的动物被安置在EE中2周,而另外50%的动物仍被安置在标准住房(SH)中。在这一阶段结束时,我们评估了内脏和躯体的敏感性。我们还收集结肠组织测量结肠通透性。从CeA和海马组织中分离微孔,测定GR表达。未暴露于WAS的对照动物在研究期间保持在SH中(每组n = 8)。结果在雄性和雌性大鼠中,EE均能逆转应激诱导的内脏(p <0.001)和躯体(p <0.01),与被置于SH环境中的WAS动物相比,过敏程度与对照动物相当。EE暴露也逆转了海马中GR表达的变化(p <0.01)和CeA (p <0.01),使GR表达正常化至控制水平。EE暴露可改善应激性结肠高通透性(p <0.01)和女性(p <结论我们的研究结果表明,行为疗法是治疗IBS的可行选择,因为它们可以对抗应激诱导的IBS症状的病理生理,包括内脏过敏、结肠通透性增加和基因表达改变。
{"title":"Environmental enrichment reverses stress-induced changes in the brain-gut axis to ameliorate chronic visceral and somatic hypersensitivity","authors":"A. Orock ,&nbsp;A.C. Johnson ,&nbsp;E. Mohammadi ,&nbsp;B. Greenwood-Van Meerveld","doi":"10.1016/j.ynstr.2023.100590","DOIUrl":"https://doi.org/10.1016/j.ynstr.2023.100590","url":null,"abstract":"<div><h3>Introduction</h3><p>Behavioral therapies, including cognitive behavioral therapy, hypnotherapy and stress management activities, have emerged as effective treatments for irritable bowel syndrome (IBS), a female predominant disorder of the brain-gut axis. IBS, affecting over 10% of the global population, typically presents with abnormal bowel habits and abdominal pain due to visceral hypersensitivity. While the mechanisms underlying how behavioral therapies treat IBS are still elusive, we had previously shown that chronic stress alters gene expression in brain regions critical for stress processing and nociception. We found that exposure to an enriched environment (EE), the rodent analogue of behavioral therapies, prior to and during the stressor was sufficient to <u>prevent</u> stress-induced changes in glucocorticoid receptor (GR) expression in the central nucleus of the amygdala (CeA) and hippocampus. Pre-exposure to EE also inhibited stress-induced increased colonic permeability and was able to block the induction of stress-induced visceral and somatic hypersensitivity. However, it remains unknown if EE can <u>reverse</u> chronic viscerosomatic hypersensitivity that persists following exposure to stress. We hypothesized that EE after chronic stress would be sufficient to reverse stress-induced changes in i) GR expression in the CeA and hippocampus, ii) ameliorate stress-induced colonic hyperpermeability and iii) restore normal visceral and somatic sensitivity in male and female rats.</p></div><div><h3>Methods</h3><p>Male and female rats were exposed to daily water avoidance stress (WAS). After confirming the rats had developed visceral hypersensitivity, 50% of the animals were housed in EE for 2 weeks while the other 50% remained in standard housing (SH). At the end of this period, we assessed visceral and somatic sensitivity. We also collected colon tissue to measure colonic permeability. Micro-punches of tissue from the CeA and hippocampus were isolated to measure GR expression. Control animals not exposed to WAS were kept in SH for the duration of the study (n = 8 per group).</p></div><div><h3>Results</h3><p>In both male and female rats, EE reversed stress-induced visceral (p &lt; 0.001) and somatic (p &lt; 0.01) hypersensitivity when compared to WAS animals housed in SH to levels comparable to control animals. EE exposure also reversed changes in GR expression in both the hippocampus (p &lt; 0.01) and CeA (p &lt; 0.01), normalizing GR expression to control levels. EE exposure ameliorated stress-induced colonic hyperpermeability in both male (p &lt; 0.01) and female (p &lt; 0.01) rats compared to WAS rats in SH.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that behavioral therapies are viable therapeutic options for IBS as they can counter the stress-induced pathophysiology underlying IBS symptoms including visceral hypersensitivity, increased colonic permeability and altered gene expression.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000784/pdfft?md5=50ec445d3b2bac68d749ce29cffc7d14&pid=1-s2.0-S2352289523000784-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138466303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microglia are necessary for probiotics supplementation to improve impaired fear extinction caused by pregnancy stress in adult offspring of rats 小胶质细胞是补充益生菌改善大鼠成年后代妊娠应激引起的恐惧消退障碍所必需的
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-19 DOI: 10.1016/j.ynstr.2023.100591
Ru Zeng , Jie Chen , Yihan Peng , Weiye Xu , Yuanyuan Tao , Min Li , Ruqi Zhang , Jingzhuo Meng , Zhiyuan Li , Leping Zeng , Jufang Huang

The prevention and treatment of fear-related disorders in offspring affected by pregnancy stress remains challenging at clinic. Here, we examined the effects of gut microbiota of stressed pregnant rats on the fear extinction of their offsprings, and the potential mechanisms. We found that gut microbiota transplantation from rats with pregnancy stress to normal pregnant rats impaired fear extinction, induced microglial activation and synaptic phagocytosis, increased synapse loss in offsprings. Probiotics supplement during pregnancy stress partly normalized pregnancy stress-induced gut microbiota dysbiosis of pregnant rats, and promoted fear memory extinction, inhibited fear memory reappearance, and limited microglial activation and synaptic phagocytosis in offsprings. These data revealed that gut microbiota of stressed pregnant mother improved the development of fear-related disorders of offspring, which may be associated with microglial synaptic pruning.

预防和治疗受妊娠压力影响的后代的恐惧相关障碍在临床上仍然具有挑战性。在这里,我们研究了应激怀孕大鼠肠道微生物群对其后代恐惧灭绝的影响及其潜在机制。我们发现,将妊娠应激大鼠的肠道菌群移植到正常妊娠大鼠的后代中,会损害恐惧消退,诱导小胶质细胞激活和突触吞噬,增加突触损失。妊娠应激期间补充益生菌可部分缓解妊娠应激引起的妊娠大鼠肠道菌群失调,促进后代恐惧记忆消退,抑制恐惧记忆重现,限制小胶质细胞激活和突触吞噬。这些数据表明,压力孕妇的肠道微生物群改善了后代恐惧相关疾病的发展,这可能与小胶质突触修剪有关。
{"title":"Microglia are necessary for probiotics supplementation to improve impaired fear extinction caused by pregnancy stress in adult offspring of rats","authors":"Ru Zeng ,&nbsp;Jie Chen ,&nbsp;Yihan Peng ,&nbsp;Weiye Xu ,&nbsp;Yuanyuan Tao ,&nbsp;Min Li ,&nbsp;Ruqi Zhang ,&nbsp;Jingzhuo Meng ,&nbsp;Zhiyuan Li ,&nbsp;Leping Zeng ,&nbsp;Jufang Huang","doi":"10.1016/j.ynstr.2023.100591","DOIUrl":"https://doi.org/10.1016/j.ynstr.2023.100591","url":null,"abstract":"<div><p>The prevention and treatment of fear-related disorders in offspring affected by pregnancy stress remains challenging at clinic. Here, we examined the effects of gut microbiota of stressed pregnant rats on the fear extinction of their offsprings, and the potential mechanisms. We found that gut microbiota transplantation from rats with pregnancy stress to normal pregnant rats impaired fear extinction, induced microglial activation and synaptic phagocytosis, increased synapse loss in offsprings. Probiotics supplement during pregnancy stress partly normalized pregnancy stress-induced gut microbiota dysbiosis of pregnant rats, and promoted fear memory extinction, inhibited fear memory reappearance, and limited microglial activation and synaptic phagocytosis in offsprings. These data revealed that gut microbiota of stressed pregnant mother improved the development of fear-related disorders of offspring, which may be associated with microglial synaptic pruning.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000796/pdfft?md5=e710c23c4a633a8410c0bb1d69314fa0&pid=1-s2.0-S2352289523000796-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138389975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between gut microbiota and its functional metabolites with prenatal depression in women 肠道菌群及其功能代谢物与妇女产前抑郁症的关系
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-17 DOI: 10.1016/j.ynstr.2023.100592
Tianqu Xie , Xiaoxiao Fan , Hanghang Pang , Tianzi Zang , Ni Wu , Juan Liu , Ziying Li , Sha Li , Quanfei Zhu , Julia Elise Slack , Jinbing Bai , Yu Xu , Yanqun Liu

Background

The gut microbiota may affect mood through the microbiota-gut-brain axis. The purpose of this study was to examine the effect of the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), on prenatal depression and to determine the role of 5-hydroxytryptamine (5-HT) on prenatal depression in association with the gut microbiota and its metabolites (i.e. SCFAs).

Methods

Eighty-six pregnant women in the third trimester were recruited. Prenatal depression was determined by a score of 10 via the Edinburgh Postpartum Depression Scale. Demographic data, stool, and blood samples were collected. The gut microbiota and its metabolites SCFAs were determined by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry analysis. Plasma 5-HT was determined by gas chromatography-mass spectrometry analysis.

Results

After controlling relevant covariates, our results found the higher the abundance of Candidatus_Soleaferrea, the lower the risk of prenatal depression; the higher the concentration of propanoic acid, the higher risk of prenatal depression. Our results also found the lower the plasma 5-HT, the higher the risk of prenatal depression, and 5-HT was related to unclassified_c_Clostridia and NK4A214_group. However, results of this study did not support the moderating effect of plasma 5-HT on the association of Candidatus_Soleaferrea or propionic acid with prenatal depression.

Conclusions

Results of this study supported that changes in certain gut microbiota, SCFAs, and plasma 5-HT during pregnancy were associated with prenatal depression. This finding provides new ideas for interventions based on diet or probiotics to regulate mood during pregnancy.

肠道菌群可能通过菌群-肠-脑轴影响情绪。本研究的目的是研究肠道微生物群及其代谢物,如短链脂肪酸(SCFAs)对产前抑郁症的影响,并确定5-羟色胺(5-HT)在与肠道微生物群及其代谢物(即SCFAs)相关的产前抑郁症中的作用。方法选取孕晚期孕妇86例。产前抑郁是通过爱丁堡产后抑郁量表以10分来确定的。收集了人口统计资料、粪便和血液样本。采用16S rRNA基因测序和液相色谱-质谱分析方法测定肠道菌群及其代谢产物SCFAs。采用气相色谱-质谱法测定血浆5-羟色胺含量。结果在控制相关变量后发现,Candidatus_Soleaferrea丰度越高,产前抑郁风险越低;丙酸浓度越高,产前抑郁的风险越高。我们的研究结果还发现,血浆5-HT越低,产前抑郁的风险越高,5-HT与unclassified_c_Clostridia和NK4A214_group有关。然而,本研究结果不支持血浆5-羟色胺在Candidatus_Soleaferrea或丙酸与产前抑郁的关联中的调节作用。结论妊娠期某些肠道菌群、scfa和血浆5-羟色胺的变化与产前抑郁有关。这一发现为基于饮食或益生菌的干预来调节怀孕期间的情绪提供了新的思路。
{"title":"Association between gut microbiota and its functional metabolites with prenatal depression in women","authors":"Tianqu Xie ,&nbsp;Xiaoxiao Fan ,&nbsp;Hanghang Pang ,&nbsp;Tianzi Zang ,&nbsp;Ni Wu ,&nbsp;Juan Liu ,&nbsp;Ziying Li ,&nbsp;Sha Li ,&nbsp;Quanfei Zhu ,&nbsp;Julia Elise Slack ,&nbsp;Jinbing Bai ,&nbsp;Yu Xu ,&nbsp;Yanqun Liu","doi":"10.1016/j.ynstr.2023.100592","DOIUrl":"https://doi.org/10.1016/j.ynstr.2023.100592","url":null,"abstract":"<div><h3>Background</h3><p>The gut microbiota may affect mood through the microbiota-gut-brain axis. The purpose of this study was to examine the effect of the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), on prenatal depression and to determine the role of 5-hydroxytryptamine (5-HT) on prenatal depression in association with the gut microbiota and its metabolites (i.e. SCFAs).</p></div><div><h3>Methods</h3><p>Eighty-six pregnant women in the third trimester were recruited. Prenatal depression was determined by a score of 10 via the Edinburgh Postpartum Depression Scale. Demographic data, stool, and blood samples were collected. The gut microbiota and its metabolites SCFAs were determined by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry analysis. Plasma 5-HT was determined by gas chromatography-mass spectrometry analysis.</p></div><div><h3>Results</h3><p>After controlling relevant covariates, our results found the higher the abundance of <em>Candidatus_Soleaferrea</em>, the lower the risk of prenatal depression; the higher the concentration of propanoic acid, the higher risk of prenatal depression. Our results also found the lower the plasma 5-HT, the higher the risk of prenatal depression, and 5-HT was related to <em>unclassified_c_Clostridia</em> and <em>NK4A214_group</em>. However, results of this study did not support the moderating effect of plasma 5-HT on the association of <em>Candidatus_Soleaferrea</em> or propionic acid with prenatal depression.</p></div><div><h3>Conclusions</h3><p>Results of this study supported that changes in certain gut microbiota, SCFAs, and plasma 5-HT during pregnancy were associated with prenatal depression. This finding provides new ideas for interventions based on diet or probiotics to regulate mood during pregnancy.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000802/pdfft?md5=98763d2ddddb880078f3d3989f5c1218&pid=1-s2.0-S2352289523000802-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138413481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Imbalanced glucocorticoid and mineralocorticoid stress hormone receptor function has sex-dependent and independent regulatory effects in the mouse hippocampus 糖皮质激素和矿皮质激素应激激素受体功能失衡在小鼠海马中具有性别依赖和独立的调节作用
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-17 DOI: 10.1016/j.ynstr.2023.100589
Robert H. Oakley , Natallia V. Riddick , Sheryl S. Moy , John A. Cidlowski

Many stress-related neuropsychiatric disorders display pronounced sex differences in their frequency and clinical symptoms. Glucocorticoids are primary stress hormones that have been implicated in the development of these disorders but whether they contribute to the observed sex bias is poorly understood. Glucocorticoids signal through two closely related nuclear receptors, the glucocorticoid (GR) and mineralocorticoid receptor (MR). To elucidate the sex-specific and independent actions of glucocorticoids in the hippocampus, we developed knockout mice lacking hippocampal GR, MR, or both GR and MR. Mice deficient in hippocampal MR or both GR and MR showed an altered molecular phenotype of CA2 neurons and reduced anxiety-like behavior in both sexes, but altered stress adaptation behavior only in females and enhanced fear-motivated cue learning only in males. All three knockout mouse models displayed reduced sociability but only in male mice. Male and female mice deficient in both hippocampal GR and MR exhibited extensive neurodegeneration in the dentate gyrus. Global transcriptomic analysis revealed a marked expansion in the number of dysregulated genes in the hippocampus of female knockout mice compared to their male counterparts; however, the overall patterns of gene dysregulation were remarkably similar in both sexes. Within and across sex comparisons identified key GR and MR target genes and associated signaling pathways underlying the knockout phenotypes. These findings define major sex-dependent and independent effects of GR/MR imbalances on gene expression and functional profiles in the hippocampus and inform new strategies for treating men and women with stress-related neuropsychiatric disorders.

许多与压力相关的神经精神疾病在发病频率和临床症状上表现出明显的性别差异。糖皮质激素是主要的应激激素,与这些疾病的发展有关,但它们是否有助于观察到的性别偏见尚不清楚。糖皮质激素通过两个密切相关的核受体糖皮质激素(GR)和矿皮质激素受体(MR)发出信号。为了阐明糖皮质激素在海马体中的性别特异性和独立作用,我们开发了缺乏海马GR、MR或同时缺乏GR和MR的敲除小鼠,海马MR或同时缺乏GR和MR的小鼠在两性中都表现出CA2神经元分子表型的改变和焦虑样行为的减少,但仅在雌性中改变了应激适应行为,仅在雄性中增强了恐惧动机线索学习。所有三种基因敲除小鼠模型都表现出社交能力下降,但仅在雄性小鼠中。海马GR和MR均缺乏的雄性和雌性小鼠在齿状回表现出广泛的神经变性。全球转录组学分析显示,与雄性敲除小鼠相比,雌性敲除小鼠海马中失调基因的数量显着增加;然而,基因失调的总体模式在两性中是非常相似的。性别内部和跨性别比较确定了关键的GR和MR靶基因以及敲除表型的相关信号通路。这些发现确定了GR/MR失衡对海马体基因表达和功能谱的主要性别依赖和独立影响,并为治疗男性和女性压力相关神经精神疾病提供了新的策略。
{"title":"Imbalanced glucocorticoid and mineralocorticoid stress hormone receptor function has sex-dependent and independent regulatory effects in the mouse hippocampus","authors":"Robert H. Oakley ,&nbsp;Natallia V. Riddick ,&nbsp;Sheryl S. Moy ,&nbsp;John A. Cidlowski","doi":"10.1016/j.ynstr.2023.100589","DOIUrl":"https://doi.org/10.1016/j.ynstr.2023.100589","url":null,"abstract":"<div><p>Many stress-related neuropsychiatric disorders display pronounced sex differences in their frequency and clinical symptoms. Glucocorticoids are primary stress hormones that have been implicated in the development of these disorders but whether they contribute to the observed sex bias is poorly understood. Glucocorticoids signal through two closely related nuclear receptors, the glucocorticoid (GR) and mineralocorticoid receptor (MR). To elucidate the sex-specific and independent actions of glucocorticoids in the hippocampus, we developed knockout mice lacking hippocampal GR, MR, or both GR and MR. Mice deficient in hippocampal MR or both GR and MR showed an altered molecular phenotype of CA2 neurons and reduced anxiety-like behavior in both sexes, but altered stress adaptation behavior only in females and enhanced fear-motivated cue learning only in males. All three knockout mouse models displayed reduced sociability but only in male mice. Male and female mice deficient in both hippocampal GR and MR exhibited extensive neurodegeneration in the dentate gyrus. Global transcriptomic analysis revealed a marked expansion in the number of dysregulated genes in the hippocampus of female knockout mice compared to their male counterparts; however, the overall patterns of gene dysregulation were remarkably similar in both sexes. Within and across sex comparisons identified key GR and MR target genes and associated signaling pathways underlying the knockout phenotypes. These findings define major sex-dependent and independent effects of GR/MR imbalances on gene expression and functional profiles in the hippocampus and inform new strategies for treating men and women with stress-related neuropsychiatric disorders.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289523000772/pdfft?md5=344f9cda245515e0d012ae2832a64ce0&pid=1-s2.0-S2352289523000772-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138389974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Neurobiology of Stress
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1