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Elevated GABAergic neurotransmission prevents chronic intermittent ethanol induced hyperexcitability of intrinsic and extrinsic inputs to the ventral subiculum of female rats GABA 能神经递质的增加可防止慢性间歇性乙醇诱导的雌性大鼠腹腔下丘脑内在和外在输入的过度兴奋性
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-10 DOI: 10.1016/j.ynstr.2024.100665
Eva C. Bach, Jeff L. Weiner

With the recent rise in the rate of alcohol use disorder (AUD) in women, the historical gap between men and women living with this condition is narrowing. While there are many commonalities in how men and women are impacted by AUD, an accumulating body of evidence is revealing sex-dependent adaptations that may require distinct therapeutic approaches. Preclinical rodent studies are beginning to shed light on sex differences in the effects of chronic alcohol exposure on synaptic activity in a number of brain regions. Prior studies from our laboratory revealed that, while withdrawal from chronic intermittent ethanol (CIE), a commonly used model of AUD, increased excitability in the ventral hippocampus (vHC) of male rats, this same treatment had the opposite effect in females. A follow-up study not only expanded on the synaptic mechanisms of these findings in male rats, but also established a CIE-dependent increase in the excitatory-inhibitory (E-I) balance of a glutamatergic projection from the basolateral amygdala to vHC (BLA-vHC). This pathway modulates anxiety-like behavior and could help explain the comorbid occurrence of anxiety disorders in individuals suffering from AUD. The present study sought to conduct a similar analysis of CIE effects on both synaptic mechanisms in the vHC and adaptations in the BLA-vHC pathway of female rats. Our findings indicate that CIE increases the strength of inhibitory neurotransmission in the vHC and that this sex-specific adaptation blocks, or at least delays, the increases in intrinsic vHC excitability and BLA-vHC synaptic transmission observed in males. Our findings establish the BLA-vHC pathway and the vHC as important circuitry to consider for future studies directed at identifying sex-dependent therapeutic approaches to AUD.

随着近年来女性酒精使用障碍(AUD)发病率的上升,男女患者之间的历史差距正在缩小。虽然男性和女性受 AUD 影响的方式有许多共同之处,但不断积累的证据显示,性别依赖性适应可能需要不同的治疗方法。临床前啮齿动物研究开始揭示慢性酒精暴露对多个脑区突触活动影响的性别差异。我们实验室之前的研究发现,慢性间歇性乙醇(CIE)是一种常用的 AUD 模型,它能提高雄性大鼠腹侧海马(vHC)的兴奋性,而同样的治疗方法对雌性大鼠的影响却恰恰相反。一项后续研究不仅扩展了这些发现在雄性大鼠中的突触机制,还确定了从杏仁基底外侧到vHC(BLA-vHC)的谷氨酸能投射的兴奋-抑制(E-I)平衡的增加依赖于乙醇胺。该通路可调节焦虑样行为,有助于解释 AUD 患者合并焦虑症的原因。本研究试图对CIE对雌性大鼠vHC突触机制和BLA-vHC通路适应性的影响进行类似的分析。我们的研究结果表明,CIE增加了vHC中抑制性神经传递的强度,这种性别特异性适应阻断或至少延缓了在雄性大鼠身上观察到的vHC内在兴奋性和BLA-vHC突触传递的增加。我们的研究结果证明,BLA-vHC通路和vHC是未来研究中需要考虑的重要回路,这些研究旨在确定治疗AUD的性别依赖性治疗方法。
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引用次数: 0
Vicarious heterosexism-based stress induces alcohol, nicotine, and cannabis craving and negative affect among sexual minority young adults: An experimental study 基于模仿异性恋的压力会诱发性少数群体年轻人对酒精、尼古丁和大麻的渴求以及负面情绪:一项实验研究
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-10 DOI: 10.1016/j.ynstr.2024.100668
Ethan H. Mereish , Robert Miranda Jr.

Purpose

Sexual minority young adults are at increased risk for hazardous drinking and alcohol use disorder compared to heterosexual adults. Heterosexism-based stressors contribute and often explain inequities in alcohol outcomes. However, the extant research primarily relies on correlational designs, and often neglects the importance of alcohol craving, despite its foundational role in addiction. Leveraging a novel experimental mood induction paradigm, this study examined the effects of exposure to vicarious heterosexism-based stress on alcohol craving and negative affect among sexual minority young adults who drink heavily. We also examined its effects on cannabis and nicotine craving among participants who used cannabis and nicotine, respectively. Lastly, we examined moderating factors that could influence the impact of exposure to heterosexism-based stress on alcohol craving.

Methods

Participants were 101 heavy drinking sexual minority young adults, ages 20–35 (M = 26.46 years old; SD = 3.49), recruited from the community (51.5% female sex assigned at birth; 76.3% cisgender; 51.5% plurisexual; and 42.6% racial and ethnic minorities). They completed three mood induction trials counterbalanced over three visits on different days: heterosexism stress, general stress, and neutral. Structured interviews assessed criteria for DSM-5 alcohol use disorder (AUD) and substance use, and self-report measures assessed lifetime traumatic stressors.

Results

Most participants met criteria for past-year AUD (74.7%). Exposure to heterosexism stress produced more negative affect and substance craving than the neutral mood induction, even while controlling for demographic variables and lifetime exposure to traumatic and heterosexism stressors. Exposure to heterosexism-based stress had large effects on alcohol craving among participants who had greater drinking to cope motives and heterosexism-specific rejection sensitivity, whereas the effects were small for those who had lower drinking to cope motives and heterosexism-specific rejection sensitivity. Demographic, lifetime stress, prior alcohol use, and AUD symptom severity variables were not significant moderators. Greater substance craving induced by heterosexism-based stress in the laboratory was associated with greater recent and current substance use.

Conclusions

This study findings show that vicarious exposure to heterosexism elicits negative mood and alcohol, cannabis, and nicotine craving among sexual minority young adults who engaged in heavy drinking. The effects for alcohol craving were largest among those who endorse high levels of drinking to cope motives and heterosexism-based rejection sensitivity. These findings have implications for oppression-based stress and motivational models of addiction.

目的与异性恋成年人相比,性少数群体的年轻人酗酒和酒精使用障碍的风险更高。基于异性恋主义的压力因素导致了酒精结果的不平等,而且往往可以解释这种不平等。然而,现有的研究主要依赖于相关性设计,往往忽视了酒精渴求的重要性,尽管酒精渴求在成瘾中起着基础性作用。本研究利用一种新颖的实验性情绪诱导范式,考察了暴露于替代性异性恋压力对酗酒的性少数群体年轻人的酒精渴求和负面情绪的影响。我们还研究了它对吸食大麻和尼古丁的参与者的大麻和尼古丁渴求的影响。最后,我们研究了可能影响暴露于异性恋压力对酒精渴求的影响的调节因素。方法参与者是 101 名酗酒的性少数群体年轻人,年龄在 20-35 岁之间(M = 26.46 岁;SD = 3.49),他们是从社区招募来的(51.5% 为出生时性别分配的女性;76.3% 为顺性性别;51.5% 为多性性别;42.6% 为少数种族和少数民族)。他们在不同日期的三次访问中完成了三种情绪诱导试验:异性恋压力、一般压力和中性。结构化访谈评估了 DSM-5 酒精使用障碍(AUD)和药物使用的标准,自我报告测量评估了一生中的创伤性压力源。与中性情绪诱导相比,暴露于异性恋压力会产生更多的负面情绪和药物渴求,即使在控制了人口统计学变量和终生暴露于创伤和异性恋压力源的情况下也是如此。暴露于异性恋压力对饮酒应付动机和异性恋拒绝敏感性较高的参与者的酒精渴求影响较大,而对饮酒应付动机和异性恋拒绝敏感性较低的参与者的影响较小。人口统计学变量、终生压力变量、先前饮酒变量和 AUD 症状严重程度变量都没有显著的调节作用。本研究结果表明,在大量饮酒的性少数群体年轻人中,异性恋主义的替代性暴露会引发负面情绪以及对酒精、大麻和尼古丁的渴求。对酒精渴求的影响在那些赞同高水平饮酒以应对动机和基于异性恋排斥敏感性的人群中最大。这些发现对基于压迫的压力和成瘾动机模型有一定的启示。
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引用次数: 0
DCC, a potential target for controlling fear memory extinction and hippocampal LTP in male mice receiving single prolonged stress DCC是控制接受单次长期应激的雄性小鼠恐惧记忆消退和海马LTP的潜在靶标
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-08-08 DOI: 10.1016/j.ynstr.2024.100666
Shaojie Yang , Jiamin Hu , Yuzhuang Chen , Zhengrong Zhang , Jingji Wang , Guoqi Zhu

Post-traumatic stress disorder (PTSD) is a severe stress-dependent psychiatric disorder characterized by impairment of fear memory extinction; however, biological markers to determine impaired fear memory extinction in PTSD remain unclear. In male mice with PTSD-like behaviors elicited by single prolonged stress (SPS), 19 differentially expressed proteins in the hippocampus were identified compared with controls. Among them, a biological macromolecular protein named deleted in colorectal cancer (DCC) was highly upregulated. Specific overexpression of DCC in the hippocampus induced similar impairment of long-term potentiation (LTP) and fear memory extinction as observed in SPS mice. The impairment of fear memory extinction in SPS mice was improved by inhibiting the function of hippocampal DCC using a neutralizing antibody. Mechanistic studies have shown that knocking down or inhibiting μ-calpain in hippocampal neurons increased DCC expression and induced impairment of fear memory extinction. Additionally, SPS-triggered impairment of hippocampal LTP and fear memory extinction could be rescued through activation of the Rac1–Pak1 signaling pathway. Our study provides evidence that calpain-mediated regulation of DCC controls hippocampal LTP and fear memory extinction in SPS mice, which likely through activation of the Rac1–Pak1 signaling pathway.

创伤后应激障碍(PTSD)是一种严重的应激依赖性精神障碍,其特征是恐惧记忆消退功能受损;然而,确定创伤后应激障碍中恐惧记忆消退功能受损的生物标志物仍不清楚。在单次长期应激(SPS)诱发的具有类似创伤后应激障碍行为的雄性小鼠中,与对照组相比,海马中发现了19种不同表达的蛋白质。其中,一种名为 "结肠直肠癌中删除"(DCC)的生物大分子蛋白被高度上调。DCC在海马中的特异性过表达诱导了与在SPS小鼠中观察到的类似的长时程电位(LTP)和恐惧记忆消退损伤。通过使用中和抗体抑制海马 DCC 的功能,SPS 小鼠的恐惧记忆消除功能受损情况得到了改善。机理研究表明,敲除或抑制海马神经元中的μ-钙蛋白酶会增加DCC的表达,并诱导恐惧记忆的减弱。此外,通过激活 Rac1-Pak1 信号通路,可以挽救 SPS 触发的海马 LTP 和恐惧记忆消退损伤。我们的研究提供了证据,证明钙蛋白酶介导的对DCC的调节控制了SPS小鼠的海马LTP和恐惧记忆消退,而这很可能是通过激活Rac1-Pak1信号通路实现的。
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引用次数: 0
Endocannabinoid and neuroplasticity-related changes as susceptibility factors in a rat model of posttraumatic stress disorder 作为创伤后应激障碍大鼠模型易感因素的内源性大麻素和神经可塑性相关变化
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-07-25 DOI: 10.1016/j.ynstr.2024.100662
Laszlo Szente , Gyula Y. Balla , Zoltan K. Varga , Blanka Toth , Laszlo Biro , Zoltan Balogh , Matthew N. Hill , Mate Toth , Eva Mikics , Mano Aliczki

Traumatic experiences result in the development of posttraumatic stress disorder (PTSD) in 10–25% of exposed individuals. While human clinical studies suggest that susceptibility is potentially linked to endocannabinoid (eCB) signaling, neurobiological PTSD susceptibility factors are poorly understood. Employing a rat model of contextual conditioned fear, we characterized distinct resilient and susceptible subpopulations based on lasting generalized fear, a core symptom of PTSD. In these groups, we assessed i.) eCB levels by mass spectrometry and ii.) expression variations of eCB system- and iii.) neuroplasticity-related genes by real-time quantitative PCR in the circuitry relevant in trauma-induced changes. Furthermore, employing unsupervised and semi-supervised machine learning based statistical analytical models, we assessed iv.) gene expression patterns with the most robust predictive power regarding PTSD susceptibility. According to our findings, in our model, generalized fear responses occurred with sufficient variability to characterize distinct resilient and susceptible subpopulations. Resilient subjects showed elevated prelimbic and lower ventral hippocampal levels of eCB 2-arachidonoyl-glycerol (2-AG) compared to resilient and non-shocked control subjects. Ventral hippocampal 2-AG content positively correlated with the strength of fear generalization. Furthermore, susceptibility was associated with i.) prefrontal, hippocampal and amygdalar neuronal hypoactivity, ii.) marked decrease in the expression of genes of transcription factors modulating neuroplasticity and iii.) an altered expression pattern of eCB-related genes, including enzymes involved in eCB metabolism. Unsupervised and semi-supervised statistical approaches highlighted that hippocampal gene expression patterns possess strong predictive power regarding susceptibility. Taken together, the marked eCB and neuroplasticity changes in susceptible individuals associated with abnormal activity patterns in the fear circuitry possibly contribute to context coding deficits, resulting in generalized fear.

10%-25%的受创伤者会因创伤经历而患上创伤后应激障碍(PTSD)。人类临床研究表明,创伤后应激障碍的易感性可能与内源性大麻素(eCB)信号传导有关,但人们对创伤后应激障碍的神经生物学易感因素却知之甚少。我们利用大鼠情境条件性恐惧模型,根据创伤后应激障碍的核心症状--持久的广泛性恐惧,确定了不同的抗逆性亚群和易感性亚群。在这些亚群中,我们通过质谱分析评估了 i.) eCB 水平,以及 ii.) eCB 系统和 iii.) 神经可塑性相关基因的表达变化。此外,我们还利用基于无监督和半监督机器学习的统计分析模型,评估了 iv) 对创伤后应激障碍易感性具有最强预测能力的基因表达模式。根据我们的研究结果,在我们的模型中,泛化的恐惧反应具有足够的变异性,可以描述出不同的抗逆性亚群和易感性亚群。与恢复能力强的对照组和未受惊吓的对照组相比,恢复能力强的受试者表现出边缘前区 eCB 2-arachidonoyl-glycerol (2-AG) 水平升高,而海马腹侧 eCB 2-AG 水平降低。腹侧海马 2-AG 含量与恐惧泛化的强度呈正相关。此外,易感性还与以下因素有关:i.)前额叶、海马和杏仁核神经元活性低下;ii.)调节神经可塑性的转录因子基因表达明显减少;iii.)eCB 相关基因(包括参与 eCB 代谢的酶)的表达模式改变。无监督和半监督统计方法突出表明,海马基因表达模式对易感性具有很强的预测能力。综上所述,易感人群中明显的 eCB 和神经可塑性变化与恐惧回路中的异常活动模式有关,可能会导致情境编码缺陷,从而导致广泛性恐惧。
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引用次数: 0
CD4+ T-cell subsets are associated with chronic stress effects in newly diagnosed anxiety disorders CD4+ T 细胞亚群与新诊断焦虑症的慢性压力效应有关
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-07-01 DOI: 10.1016/j.ynstr.2024.100661
Bindong Dai, Tao Li, Jinya Cao, Xiaohui Zhao, Yinan Jiang, Lili Shi, Jing Wei

Aim

Prior research has indicated a connection between CD4+ T cells and the development of anxiety, but the specific CD4+ T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4+ T cell subsets and anxiety, as well as to explore whether CD4+ T cell subsets mediate the effect of chronic psychological stress on anxiety.

Methods

56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4+ T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4+ T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed.

Results

We discovered fifteen notably distinct CD4+ T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27+CD45RA Th cells, CD27+CD28+ Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4+ T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27+CD28+ Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031).

Conclusions

Drug naïve anxiety disorder patients exhibited significant alterations in numerous CD4+ T-cell subsets. Specifically, the memory subset of CD27+CD45RA Th cells and the naïve subset of CD27+CD28+ Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27+CD28+ Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.

目的已有研究表明 CD4+ T 细胞与焦虑症的发生有关,但与焦虑症有关的特定 CD4+ T 细胞亚群仍不确定。我们的研究旨在探讨不同的 CD4+ T 细胞亚群与焦虑之间的关系,并探讨 CD4+ T 细胞亚群是否介导了慢性心理压力对焦虑的影响。根据 DSM-5 诊断标准进行诊断。焦虑和抑郁症状的严重程度分别使用汉密尔顿焦虑评定量表和汉密尔顿抑郁评定量表进行评估。生活事件量表(LES)评估了慢性压力水平。CD4+ T细胞亚群采用多参数流式细胞术进行鉴定。为了评估 CD4+ T 细胞对慢性心理压力对焦虑的影响,我们采用了偏最小二乘法结构方程建模(PLS-SEM)分析。多元线性回归分析揭示了焦虑症严重程度与 CD27+CD45RA- Th 细胞、CD27+CD28+ Tregs 和生活事件量表(LES)总分之间的关系。PLS-SEM分析表明,CD4+ T细胞亚群和LES可解释80.2%的焦虑变异。此外,还观察到 CD27+CD28+ Th/Treg 细胞是 LES 对焦虑影响的反向中介(P = 0.031)。具体而言,CD27+CD45RA-Th 细胞记忆亚群和 CD27+CD28+ Treg 细胞幼稚亚群是与焦虑严重程度相关的独立因素。此外,CD27+CD28+ Th 和 Treg 细胞亚群在长期心理压力对焦虑的影响中起着重要的中介作用。
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引用次数: 0
Repeated exposure to multiple concurrent stressors alters visual processing in the adult posterior parietal cortex 重复暴露于多种并发压力源会改变成人后顶叶皮层的视觉处理能力
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-07-01 DOI: 10.1016/j.ynstr.2024.100660
Soo Bin Park, Gyorgy Lur

Chronic stress is well known to erode cognitive functions. Yet, our understanding of how repeated stress exposure impacts one of the fundamental bases of cognition: sensory processing, remains limited. The posterior parietal cortex (PPC) is a high order visual region, known for its role in visually guided decision making, multimodal integration, attention, and working memory. Here, we used functional measures to determine how repeated exposure to multiple concurrent stressors (RMS) affects sensory processing in the PPC in adult male mice. A longitudinal experimental design, repeatedly surveying the same population of neurons using in vivo two-photon imaging, revealed that RMS disrupts the balanced turnover of visually responsive cells in layer 2/3 of the PPC. Across the population, RMS-induced changes in visual responsiveness followed a bimodal distribution suggesting idiosyncratic stress effects. In cells that maintained their responsiveness across recording sessions, we found that stress reduced visual response magnitudes and feature selectivity. While we did not observe stress-induced elimination of excitatory synapses, noise correlation statistics indicated that RMS altered visual input to the neuronal population. The impact of RMS was restricted to visually evoked responses and was not evident in neuronal activity associated with locomotion onset. Together, our results indicate that despite no apparent synaptic reorganization, stress exposure in adulthood can disrupt sensory processing in the PPC, with the effects showing remarkable individual variation.

众所周知,慢性压力会侵蚀认知功能。然而,我们对重复压力暴露如何影响认知的基本基础之一:感觉处理的了解仍然有限。后顶叶皮层(PPC)是一个高阶视觉区域,因其在视觉引导决策、多模态整合、注意力和工作记忆中的作用而闻名。在这里,我们使用功能测量方法来确定反复暴露于多种并发压力源(RMS)如何影响成年雄性小鼠顶叶后皮层的感觉处理。我们采用纵向实验设计,利用双光子成像技术对同一神经元群进行了反复调查,结果发现 RMS 会破坏 PPC 第 2/3 层视觉反应细胞的平衡更替。在整个群体中,RMS诱导的视觉反应性变化呈双峰分布,表明存在特异性应激效应。在记录过程中保持反应性的细胞中,我们发现应激降低了视觉反应幅度和特征选择性。虽然我们没有观察到应激诱导的兴奋性突触消失,但噪声相关统计表明,RMS 改变了神经元群的视觉输入。RMS 的影响仅限于视觉诱发反应,在与运动开始相关的神经元活动中并不明显。总之,我们的研究结果表明,尽管没有明显的突触重组,但成年期的压力暴露会扰乱PPC的感觉处理,其影响表现出显著的个体差异。
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引用次数: 0
Heightened SAM- and HPA-axis activity during acute stress impairs decision-making: A systematic review on underlying neuropharmacological mechanisms 急性应激时SAM和HPA轴活动增强会损害决策:关于潜在神经药理学机制的系统综述
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-07-01 DOI: 10.1016/j.ynstr.2024.100659
Lukas van Herk , Frank P.M. Schilder , Antoin D. de Weijer , Bastiaan Bruinsma , Elbert Geuze

Individuals might be exposed to intense acute stress while having to make decisions with far-reaching consequences. Acute stress impairs processes required for decision-making by activating different biological stress cascades that in turn affect the brain. By knowing which stress system, brain areas, and receptors are responsible for compromised decision-making processes, we can effectively find potential pharmaceutics that can prevent the deteriorating effects of acute stress. We used a systematic review procedure and found 44 articles providing information on this topic. Decision-making processes could be subdivided into 4 domains (cognitive, motivational, affective, and predictability) and could be referenced to specific brain areas, while mostly being impaired by molecules associated with the sympathetic-adrenal-medullar and hypothalamic-pituitary-adrenal axes. Potential drugs to alleviate these effects included α1 and β adrenoceptor antagonists, α2 adrenoceptor agonists, and corticotropin releasing factor receptor1/2 antagonists, while consistent stress-like effects were found with yohimbine, an α2 adrenoceptor antagonist. We suggest possible avenues for future research.

人在做出具有深远影响的决策时,可能会面临强烈的急性压力。急性应激会激活不同的生物应激级联,进而影响大脑,从而损害决策所需的过程。通过了解哪种应激系统、大脑区域和受体会导致决策过程受损,我们就能有效地找到潜在的药物,防止急性应激的恶化效应。我们采用了系统性综述程序,发现有 44 篇文章提供了有关这一主题的信息。决策过程可细分为 4 个领域(认知、动机、情感和可预测性),并可参考特定的脑区,而大部分决策过程都会受到与交感-肾上腺-髓质轴和下丘脑-垂体-肾上腺轴相关的分子的影响。缓解这些效应的潜在药物包括α和β肾上腺素受体拮抗剂、α肾上腺素受体激动剂和促肾上腺皮质激素释放因子受体拮抗剂,而α肾上腺素受体拮抗剂育亨宾则具有一致的应激样效应。我们提出了未来研究的可能途径。
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引用次数: 0
The role of objective sleep in implicit and explicit affect regulation: A comprehensive review 客观睡眠在隐性和显性情绪调节中的作用:全面回顾
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-07-01 DOI: 10.1016/j.ynstr.2024.100655
Laura D. Straus , Maia ten Brink , Pilleriin Sikka , Radhika Srivastava , James J. Gross , Peter J. Colvonen

Impairments in sleep and affect regulation are evident across a wide range of mental disorders. Understanding the sleep factors that relate to affect regulatory difficulties will inform mechanistic understanding and aid in treatment. Despite rising interest, some research challenges in this area include integrating across different clinical and non-clinical literatures investigating the role of sleep architecture (measured with polysomnography) and experimentally manipulated sleep, as well as integrating more explicit versus implicit affect regulation processes. In this comprehensive review, we use a unifying framework to examine sleep's relationship with implicit-automatic regulation and explicit-controlled regulation, both of which are relevant to mental health (e.g., PTSD and depression). Many studies of implicit-automatic regulation (e.g., fear extinction and safety learning) demonstrate the importance of sleep, and REM sleep specifically. Studies of explicit-controlled regulation (e.g., cognitive reappraisal and expressive suppression) are less consistent in their findings, with results differing depending on the type of affect regulation and/or way that sleep was measured or manipulated. There is a clear relationship between objective sleep and affect regulation processes. However, there is a need for 1) more studies focusing on sleep and explicit-controlled affect regulation; 2) replication with the same types of regulation strategies; 3) more studies experimentally manipulating sleep to examine its impact on affect regulation and vice versa in order to infer cause and effect; and 4) more studies looking at sleep's impact on next-day affect regulation (not just overnight change in affect reactivity).

睡眠和情感调节障碍在多种精神障碍中都很明显。了解与情绪调节障碍有关的睡眠因素将有助于从机理上理解并帮助治疗。尽管人们对这一领域的兴趣与日俱增,但这一领域的研究仍面临一些挑战,包括整合不同的临床和非临床文献,研究睡眠结构(通过多导睡眠图测量)和实验操纵睡眠的作用,以及整合更多显性和隐性的情感调节过程。在这篇综合综述中,我们使用一个统一的框架来研究睡眠与内隐-自动调节和外显-控制调节之间的关系,这两者都与心理健康(如创伤后应激障碍和抑郁症)有关。许多关于内隐自动调节(如恐惧消退和安全学习)的研究都证明了睡眠,特别是快速眼动睡眠的重要性。关于显性控制调节(如认知重评和表达抑制)的研究结果则不太一致,其结果因情感调节的类型和/或睡眠的测量或操纵方式而异。客观睡眠与情绪调节过程之间存在明确的关系。然而,还需要:1)更多关注睡眠和明确控制的情绪调节的研究;2)使用相同类型的调节策略进行重复研究;3)更多通过实验操纵睡眠的研究,以考察睡眠对情绪调节的影响,反之亦然,从而推断因果关系;4)更多考察睡眠对第二天情绪调节影响的研究(而不仅仅是一夜之间情绪反应性的变化)。
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引用次数: 0
Stress in pregnancy - Implications for fetal BDNF in amniotic fluid at birth 孕期压力--对胎儿出生时羊水中 BDNF 的影响
IF 4.3 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-07-01 DOI: 10.1016/j.ynstr.2024.100658
Eva Kathrin Lamadé , Bruno Pedraz-Petrozzi , Ole Lindner , Pascal Meininger , Antonia Pisters , Maria Gilles , Stephanie H. Witt , Marcella Rietschel , Helene Dukal , Fabian Schunk , Michaela Coenen , Stefan A. Wudy , Rainer Hellweg , Michael Deuschle

Introduction

At the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested.

Methods

Women near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth.

Results

In bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = −0.519, p < 0.001), length per gestational age (r = −0.374, p = 0.023), head circumference per gestational age (r = −0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R2 = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders.

Conclusion

Glucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The analysis of additional fetal growth factors and inflammation upon maternal stress in further biomaterials such as the placenta is warranted, to understand mechanistic alterations of how maternal stress links to fetal development and an increased vulnerability for psychopathology.

在妊娠期的母胎界面上,妊娠期的压力会导致胎儿日后更容易出现精神病态。这种关联的潜在介导因素目前还鲜有研究,其中可能包括胎儿脑源性神经营养因子(BDNF)的早期改变。羊水对胎儿内分泌改变的影响尤其值得关注,因为在羊水中进行评估可以测量一个时间整体。本研究假设,母亲的心理测量、社会经济地位和糖皮质激素与出生时羊水中的 BDNF 水平有关。研究还检验了胎儿 BDNF 与新生儿人体测量的关系。研究对象为接受选择性剖宫产的临产妇女及其新生儿(37 人)。分析了产妇的心理测量、社会经济状况和出生时羊水中的糖皮质激素(皮质醇和可的松的总和)与胎儿出生时羊水中 BDNF 的关系。新生儿的人体测量指标包括身长、体重、头围和出生时的胎龄。在双变量分析中,母亲的心理测量和社会经济地位与胎儿出生时羊水中的BDNF无关。皮质醇和可的松的总和与胎儿出生时羊水中 BDNF 的增加有关(r = 0.745,p < 0.001)。羊水中的BDNF与胎儿每胎龄出生体重(r = -0.519,p < 0.001)、每胎龄身长(r = -0.374,p = 0.023)、每胎龄头围(r = -0.508,p = 0.001)呈负相关,但与出生时胎龄无关。在多元回归分析中,当控制了胎儿性别和母体年龄后,皮质醇和可的松的总和(p < 0.001)以及每个胎龄的出生体重(p = 0.012)与胎儿出生时羊水中较高的 BDNF 水平有关(R = 0.740,p < 0.001)。在控制了混杂因素后,每胎龄头围对胎儿BDNF的预测具有边缘显著性(p = 0.058)。羊水中的糖皮质激素与胎儿出生时的高BDNF呈正相关,这可能是胎儿的一种适应性反应。母亲的心理变量和社会经济地位与胎儿的BDNF没有联系。出生体重和每胎龄头围与胎儿出生时的BDNF成反比,这可能是低人体测量值胎儿BDNF的补偿性上调。需要进行纵向研究,以评估孕期压力对后代发育的影响。有必要进一步分析胎盘等生物材料在母体压力下产生的其他胎儿生长因子和炎症,以了解母体压力如何与胎儿发育和心理病理学易感性增加之间的机理变化。
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引用次数: 0
Functional and morphological adaptation of medial prefrontal corticotropin releasing factor receptor 1-expressing neurons in male mice following chronic ethanol exposure 长期暴露于乙醇后雄性小鼠内侧前额叶促肾上腺皮质激素释放因子受体 1 表达神经元的功能和形态适应。
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-06-17 DOI: 10.1016/j.ynstr.2024.100657
Reesha R. Patel , Pauravi Gandhi , Kathryn Spencer , Nihal A. Salem , Chloe. M. Erikson , Vittoria Borgonetti , Roman Vlkolinsky , Larry Rodriguez , Tali Nadav , Michal Bajo , Amanda J. Roberts , R. Dayne Mayfield , Marisa Roberto

Chronic ethanol dependence and withdrawal activate corticotropin releasing factor (CRF)-containing GABAergic neurons in the medial prefrontal cortex (mPFC), which tightly regulate glutamatergic pyramidal neurons. Using male CRF1:GFP reporter mice, we recently reported that CRF1-expressing (mPFCCRF1+) neurons predominantly comprise mPFC prelimbic layer 2/3 pyramidal neurons, undergo profound adaptations following chronic ethanol exposure, and regulate anxiety and conditioned rewarding effects of ethanol. To explore the effects of acute and chronic ethanol exposure on glutamate transmission, the impact of chronic alcohol on spine density and morphology, as well as persistent changes in dendritic-related gene expression, we employed whole-cell patch-clamp electrophysiology, diOlistic labeling for dendritic spine analysis, and dendritic gene expression analysis to further characterize mPFCCRF1+ and mPFCCRF1− prelimbic layer 2/3 pyramidal neurons. We found increased glutamate release in mPFCCRF1+ neurons with ethanol dependence, which recovered following withdrawal. In contrast, we did not observe significant changes in glutamate transmission in neighboring mPFCCRF1− neurons. Acute application of 44 mM ethanol significantly reduced glutamate release onto mPFCCRF1+ neurons, which was observed across all treatment groups. However, this sensitivity to acute ethanol was only evident in mPFCCRF1− neurons during withdrawal. In line with alterations in glutamate transmission, we observed a decrease in total spine density in mPFCCRF1+ neurons during dependence, which recovered following withdrawal, while again no changes were observed in mPFCCRF− neurons. Given the observed decreases in mPFCCRF1+ stubby spines during withdrawal, we then identified persistent changes at the dendritic gene expression level in mPFCCRF1+ neurons following withdrawal that may underlie these structural adaptations. Together, these findings highlight the varying responses of mPFCCRF1+ and mPFCCRF1− cell-types to acute and chronic ethanol exposure, as well as withdrawal, revealing specific functional, morphological, and molecular adaptations that may underlie vulnerability to ethanol and the lasting effects of ethanol dependence.

慢性乙醇依赖和戒断会激活内侧前额叶皮层(mPFC)中含有促肾上腺皮质激素释放因子(CRF)的GABA能神经元,而GABA能神经元会紧密调节谷氨酸能锥体神经元。最近,我们利用雄性 CRF1:GFP 报告小鼠报道了表达 CRF1 的神经元(mPFCCRF1+)主要包括 mPFC 边缘前第 2/3 层锥体神经元,在慢性乙醇暴露后会发生深刻的适应性变化,并调节乙醇的焦虑和条件奖赏效应。为了探索急性和慢性乙醇暴露对谷氨酸传递的影响、慢性酒精对脊柱密度和形态的影响以及树突相关基因表达的持续变化,我们采用了全细胞膜片钳电生理学、树突脊柱分析的逻辑标记和树突基因表达分析来进一步描述 mPFCCRF1+ 和 mPFCCRF1- 边缘前第 2/3 层锥体神经元。我们发现,乙醇依赖会导致 mPFCCRF1+ 神经元的谷氨酸释放增加,这种情况在戒断乙醇后会恢复。相比之下,我们在邻近的 mPFCCRF1- 神经元中没有观察到谷氨酸传递的显著变化。急性应用 44 毫摩尔乙醇能显著减少 mPFCCRF1+ 神经元的谷氨酸释放,这在所有治疗组中都能观察到。然而,这种对急性乙醇的敏感性仅在 mPFCCRF1- 神经元戒断时明显。与谷氨酸传递的改变一致,我们观察到在依赖期间,mPFCCRF1+神经元的脊柱总密度有所下降,但在戒断后又恢复了,而在 mPFCCRF- 神经元中同样没有观察到变化。鉴于在戒断过程中观察到的 mPFCCRF1+ 残刺的减少,我们随后确定了戒断后 mPFCCRF1+ 神经元树突基因表达水平的持续变化,这可能是这些结构适应性变化的基础。总之,这些发现突显了 mPFCCRF1+ 和 mPFCCRF1- 细胞类型对急性和慢性乙醇暴露以及戒断的不同反应,揭示了特定的功能、形态学和分子适应性,这些适应性可能是易受乙醇伤害和乙醇依赖持久影响的基础。
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Neurobiology of Stress
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