Pub Date : 2023-12-16DOI: 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.
{"title":"Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects","authors":"Katie Witkiewitz , Christian C. Garcia , 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}
Pub Date : 2023-12-15DOI: 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.
{"title":"Theta oscillatory dynamics serving cognitive control index psychosocial distress in youth","authors":"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","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}
Pub Date : 2023-12-15DOI: 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。
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Pub Date : 2023-12-07DOI: 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 , 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","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}
Pub Date : 2023-12-06DOI: 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.
{"title":"Prior experience with behavioral control over stress facilitates social dominance","authors":"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","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}
Pub Date : 2023-11-25DOI: 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.
{"title":"Glucocorticoids modulate neural activity via a rapid non-genomic effect on Kv2.2 channels in the central nervous system","authors":"Yuqi Wang , Yuchen Zhang , Jiawei Hu , Chengfang Pan , Yiming Gao , Qingzhuo Liu , Wendong Xu , Lei Xue , 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}
Pub Date : 2023-11-24DOI: 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.
{"title":"Environmental enrichment reverses stress-induced changes in the brain-gut axis to ameliorate chronic visceral and somatic hypersensitivity","authors":"A. Orock , A.C. Johnson , E. Mohammadi , 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 < 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.</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}
Pub Date : 2023-11-19DOI: 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.
{"title":"Microglia are necessary for probiotics supplementation to improve impaired fear extinction caused by pregnancy stress in adult offspring of rats","authors":"Ru Zeng , Jie Chen , Yihan Peng , Weiye Xu , Yuanyuan Tao , Min Li , Ruqi Zhang , Jingzhuo Meng , Zhiyuan Li , Leping Zeng , 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}
Pub Date : 2023-11-17DOI: 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.
{"title":"Association between gut microbiota and its functional metabolites with prenatal depression in women","authors":"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","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}
Pub Date : 2023-11-17DOI: 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.
{"title":"Imbalanced glucocorticoid and mineralocorticoid stress hormone receptor function has sex-dependent and independent regulatory effects in the mouse hippocampus","authors":"Robert H. Oakley , Natallia V. Riddick , Sheryl S. Moy , 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}