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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
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
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
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 Biochemistry, Genetics and Molecular Biology 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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引用次数: 0
Acute stress yields a sex-dependent facilitation of signaled active avoidance in rats 急性应激对大鼠主动回避信号的促进作用与性别有关
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-13 DOI: 10.1016/j.ynstr.2024.100656
Samantha L. Plas , Cecily R. Oleksiak , Claire Pitre , Chance Melton , Justin M. Moscarello , Stephen Maren

Post-traumatic stress disorder (PTSD) is a debilitating disorder characterized by excessive fear, hypervigilance, and avoidance of thoughts, situations or reminders of the trauma. Among these symptoms, relatively little is known about the etiology of pathological avoidance. Here we sought to determine whether acute stress influences avoidant behavior in adult male and female rats. We used a stress procedure (unsignaled footshock) that is known to induce long-term sensitization of fear and potentiate aversive learning. Rats were submitted to the stress procedure and, one week later, underwent two-way signaled active avoidance conditioning (SAA). In this task, rats learn to prevent an aversive outcome (shock) by performing a shuttling response when exposed to a warning signal (tone). We found that acute stress significantly enhanced SAA acquisition rate in females, but not males. Female rats exhibited significantly greater avoidance responding on the first day of training relative to controls, reaching similar levels of performance by the second day. Males that underwent the stress procedure showed similar rates of acquisition to controls but exhibited resistance to extinction. This was manifest as both elevated avoidance and intertrial responding across extinction days relative to non-stressed controls, an effect that was not observed in females. In a second experiment, acute stress sensitized footshock unconditioned responses in males, not females. However, males and females exhibited similar levels of stress-enhanced fear learning (SEFL), which was expressed as sensitized freezing to a shock-paired context. Together, these results reveal that acute stress facilitates SAA performance in both male and female rats, though the nature of this effect is different in the two sexes. We did not observe sex differences in SEFL, suggesting that the stress-induced sex difference in performance was selective for instrumental avoidance. Future work will elucidate the neurobiological mechanisms underlying the differential effect of stress on instrumental avoidance in male and female rats.

创伤后应激障碍(PTSD)是一种使人衰弱的疾病,其特征是过度恐惧、过度警惕和回避有关创伤的想法、情况或回忆。在这些症状中,人们对病理性回避的病因知之甚少。在这里,我们试图确定急性应激是否会影响成年雄性和雌性大鼠的回避行为。我们使用了一种应激程序(无信号脚震),众所周知,这种程序会诱导恐惧的长期敏感化并增强厌恶学习。大鼠在接受应激程序一周后,会接受双向信号主动回避条件反射(SAA)。在这项任务中,大鼠要学会在受到警告信号(音调)时做出穿梭反应,以防止出现厌恶结果(电击)。我们发现,急性应激会显著提高雌性大鼠的 SAA 习得率,而雄性大鼠则不会。与对照组相比,雌性大鼠在训练的第一天表现出明显更强的回避反应,到第二天则达到了相似的水平。接受压力训练的雄性大鼠表现出与对照组相似的习得率,但对消退表现出抵抗力。这表现为相对于未受应激反应的对照组,在整个消减天数内回避和试验间反应都有所提高,而在雌性动物身上却没有观察到这种效应。在第二个实验中,急性应激使雄性动物的脚震无条件反应变得敏感,而非雌性动物。然而,雄性和雌性表现出相似水平的应激增强恐惧学习(SEFL),这种学习表现为对冲击配对情境的敏感冻结。总之,这些结果表明,急性应激会促进雄性和雌性大鼠的SAA表现,但这种效应的性质在雌雄大鼠中有所不同。我们没有观察到SEFL的性别差异,这表明应激引起的性别差异对工具回避具有选择性。未来的工作将阐明压力对雌雄大鼠工具性回避产生不同影响的神经生物学机制。
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引用次数: 0
No effects of acute stress on monetary delay discounting: A systematic literature review and meta-analysis 急性压力对货币延迟贴现没有影响:系统性文献综述和元分析
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-03 DOI: 10.1016/j.ynstr.2024.100653
Paul A.G. Forbes , Jonas P. Nitschke , Nicole Hochmeister , Tobias Kalenscher , Claus Lamm

Many everyday decisions, including those concerning our health, finances and the environment, involve choosing between a smaller but imminent reward (e.g., €20 now) and a later but larger reward (e.g., €40 in a month). The extent to which an individual prefers smaller imminent rewards over larger delayed rewards can be measured using delay discounting tasks. Acute stress induces a cascade of biological and psychological responses with potential consequences for how individuals think about the future, process rewards, and make decisions, all of which can impact delay discounting. Several studies have shown that individuals focus more on imminent rewards under stress. These findings have been used to explain why individuals make detrimental choices under acute stress. Yet, the evidence linking acute stress to delay discounting is equivocal. To address this uncertainty, we conducted a meta-analysis of 11 studies (14 effects) to systematically quantify the effects of acute stress on monetary delay discounting. Overall, we find no effect of acute stress on delay discounting, compared to control conditions (SMD = −0.18, 95% CI [-0.57, 0.20], p = 0.32). We also find that neither the gender/sex of the participants, the type of stressor (e.g., physical vs. psychosocial) nor whether monetary decisions were hypothetical or incentivized (i.e. monetary decisions were actually paid out) moderated the impact of acute stress on monetary delay discounting. We argue that establishing the effects of acute stress on the separate processes involved in delay discounting, such as reward valuation and prospection, will help to resolve the inconsistencies in the field.

许多日常决策,包括与我们的健康、财务和环境有关的决策,都涉及在较小但迫在眉睫的奖励(如现在的 20 欧元)和较晚但较大的奖励(如一个月后的 40 欧元)之间做出选择。一个人在多大程度上更喜欢较小的即时奖励而不是较大的延迟奖励,可以通过延迟贴现任务来衡量。急性压力会诱发一连串的生理和心理反应,对个人思考未来、处理奖励和做出决策的方式产生潜在影响,所有这些都会影响延迟折现。多项研究表明,人在压力下会更加关注即将到来的奖励。这些研究结果被用来解释为什么人在急性压力下会做出不利的选择。然而,将急性压力与延迟折现联系起来的证据并不明确。为了解决这一不确定性,我们对 11 项研究(14 种影响)进行了荟萃分析,系统地量化了急性压力对货币延迟折现的影响。总体而言,与对照组相比,我们发现急性压力对延迟折现没有影响(SMD = -0.18,95% CI [-0.57, 0.20],p = 0.32)。我们还发现,参与者的性别、压力源的类型(如身体压力与社会心理压力)以及货币决策是假设性的还是激励性的(即货币决策是实际支付的)都不会调节急性压力对货币延迟折现的影响。我们认为,确定急性应激对延迟折现所涉及的不同过程(如奖励估值和预测)的影响将有助于解决该领域的不一致问题。
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引用次数: 0
Hyperexcitation of the glutamatergic neurons in lateral hypothalamus induced by chronic pain contributes to depression-like behavior and learning and memory impairment in male mice 慢性疼痛诱导的下丘脑外侧谷氨酸能神经元过度兴奋导致雄性小鼠出现抑郁样行为以及学习和记忆障碍
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-01 DOI: 10.1016/j.ynstr.2024.100654
Lianghui Meng , Xuefeng Zheng , Keman Xie, Yifei Li, Danlei Liu, Yuanyuan Xu, Jifeng Zhang, Fengming Wu, Guoqing Guo

Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.

慢性疼痛可诱发人类情绪紊乱和认知功能障碍,如焦虑、抑郁以及学习和记忆障碍。然而,人们对慢性疼痛引起的焦虑和抑郁样行为以及学习和记忆障碍所涉及的特定神经网络仍然知之甚少。本研究的行为测试结果表明,慢性疼痛会诱发雄性小鼠的焦虑和抑郁样行为以及学习和记忆障碍。c-Fos免疫荧光和纤维光度记录显示,慢性疼痛小鼠LH中的谷氨酸能神经元被选择性激活。接着,使用光遗传学和化学遗传学方法激活了正常小鼠 LH 的谷氨酸能神经元,结果再现了一些类似抑郁的行为以及记忆损伤,但没有再现类似焦虑的行为。最后,抑制慢性疼痛小鼠 LH 中的谷氨酸能神经元可有效缓解焦虑和抑郁样行为以及学习和记忆障碍。综上所述,我们的研究结果表明,LH 中谷氨酸能神经元的过度兴奋参与了慢性疼痛诱发的抑郁样行为以及学习和记忆损伤。
{"title":"Hyperexcitation of the glutamatergic neurons in lateral hypothalamus induced by chronic pain contributes to depression-like behavior and learning and memory impairment in male mice","authors":"Lianghui Meng ,&nbsp;Xuefeng Zheng ,&nbsp;Keman Xie,&nbsp;Yifei Li,&nbsp;Danlei Liu,&nbsp;Yuanyuan Xu,&nbsp;Jifeng Zhang,&nbsp;Fengming Wu,&nbsp;Guoqing Guo","doi":"10.1016/j.ynstr.2024.100654","DOIUrl":"10.1016/j.ynstr.2024.100654","url":null,"abstract":"<div><p>Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235228952400050X/pdfft?md5=6b0622f56c031da0a2696b424f60f254&pid=1-s2.0-S235228952400050X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141233507","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
Individual longitudinal changes in DNA-methylome identify signatures of early-life adversity and correlate with later outcome DNA-甲基组的个体纵向变化可识别早期生活逆境的特征,并与日后的结果相关联
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-31 DOI: 10.1016/j.ynstr.2024.100652
Annabel K. Short , Ryan Weber , Noriko Kamei , Christina Wilcox Thai , Hina Arora , Ali Mortazavi , Hal S. Stern , Laura Glynn , Tallie Z. Baram

Adverse early-life experiences (ELA) affect a majority of the world's children. Whereas the enduring impact of ELA on cognitive and emotional health is established, there are no tools to predict vulnerability to ELA consequences in an individual child. Epigenetic markers including peripheral-cell DNA-methylation profiles may encode ELA and provide predictive outcome markers, yet the interindividual variance of the human genome and rapid changes in DNA methylation in childhood pose significant challenges. Hoping to mitigate these challenges we examined the relation of several ELA dimensions to DNA methylation changes and outcome using a within-subject longitudinal design and a high methylation-change threshold.

DNA methylation was analyzed in buccal swab/saliva samples collected twice (neonatally and at 12 months) in 110 infants. We identified CpGs differentially methylated across time for each child and determined whether they associated with ELA indicators and executive function at age 5. We assessed sex differences and derived a sex-dependent ‘impact score’ based on sites that most contributed to methylation changes.

Changes in methylation between two samples of an individual child reflected age-related trends and correlated with executive function years later. Among tested ELA dimensions and life factors including income to needs ratios, maternal sensitivity, body mass index and infant sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, high early-life unpredictability interacted with methylation changes to presage executive function. Thus, longitudinal, within-subject changes in methylation profiles may provide a signature of ELA and a potential predictive marker of individual outcome.

早期不良生活经历(ELA)影响着世界上大多数儿童。虽然ELA对认知和情绪健康的持久影响已经得到证实,但目前还没有工具可以预测儿童个体易受ELA影响的程度。表观遗传标记(包括外周细胞 DNA 甲基化图谱)可能编码 ELA 并提供预测结果的标记,然而人类基因组的个体间差异和儿童期 DNA 甲基化的快速变化带来了巨大的挑战。为了减轻这些挑战,我们采用受试者内纵向设计和高甲基化变化阈值,研究了ELA的几个维度与DNA甲基化变化和结果的关系。我们确定了每个儿童在不同时期甲基化程度不同的 CpGs,并确定它们是否与 5 岁时的英语语言学习(ELA)指标和执行功能有关。我们评估了性别差异,并根据对甲基化变化贡献最大的位点得出了与性别相关的 "影响得分"。在经过测试的英语语言能力水平维度和生活因素(包括收入与需求比、母亲敏感性、体重指数和婴儿性别)中,父母和家庭信号的不可预测性是预测执行功能的最强因素。在女孩中,早期生活的高度不可预测性与甲基化变化相互作用,预示着执行功能。因此,甲基化特征的纵向、受试者内变化可能是ELA的特征,也是个体结果的潜在预测标志。
{"title":"Individual longitudinal changes in DNA-methylome identify signatures of early-life adversity and correlate with later outcome","authors":"Annabel K. Short ,&nbsp;Ryan Weber ,&nbsp;Noriko Kamei ,&nbsp;Christina Wilcox Thai ,&nbsp;Hina Arora ,&nbsp;Ali Mortazavi ,&nbsp;Hal S. Stern ,&nbsp;Laura Glynn ,&nbsp;Tallie Z. Baram","doi":"10.1016/j.ynstr.2024.100652","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100652","url":null,"abstract":"<div><p>Adverse early-life experiences (ELA) affect a majority of the world's children. Whereas the enduring impact of ELA on cognitive and emotional health is established, there are no tools to predict vulnerability to ELA consequences in an individual child. Epigenetic markers including peripheral-cell DNA-methylation profiles may encode ELA and provide predictive outcome markers, yet the interindividual variance of the human genome and rapid changes in DNA methylation in childhood pose significant challenges. Hoping to mitigate these challenges we examined the relation of several ELA dimensions to DNA methylation changes and outcome using a within-subject longitudinal design and a high methylation-change threshold.</p><p>DNA methylation was analyzed in buccal swab/saliva samples collected twice (neonatally and at 12 months) in 110 infants. We identified CpGs differentially methylated across time for each child and determined whether they associated with ELA indicators and executive function at age 5. We assessed sex differences and derived a sex-dependent ‘impact score’ based on sites that most contributed to methylation changes.</p><p>Changes in methylation between two samples of an individual child reflected age-related trends and correlated with executive function years later. Among tested ELA dimensions and life factors including income to needs ratios, maternal sensitivity, body mass index and infant sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, high early-life unpredictability interacted with methylation changes to presage executive function. Thus, longitudinal, within-subject changes in methylation profiles may provide a signature of ELA and a potential predictive marker of individual outcome.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000481/pdfft?md5=0cf553b631bada52c8cfef4dd0c2e6a7&pid=1-s2.0-S2352289524000481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141292366","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
Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype 青少年环境强化可诱导社会适应能力,并改变选择性培育的焦虑表型啮齿动物模型的神经基因表达
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-30 DOI: 10.1016/j.ynstr.2024.100651
Angela May O'Connor , Megan Hastings Hagenauer, Liam Cannon Thew Forrester, Pamela M. Maras, Keiko Arakawa, Elaine K. Hebda-Bauer, Huzefa Khalil, Evelyn R. Richardson, Farizah I. Rob, Yusra Sannah, Stanley J. Watson Jr., Huda Akil

Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the “internalizing” bred Low Responder (bLR) line versus the “externalizing” bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions and psychosocial stress, and how these determinants of stress response interact. Male bLR and bHR rats were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interaction and anxiety-like behavior. Adolescent enrichment caused rats to display more social interaction, as well as nominally less social avoidance, less submission during defeat, and resilience to the effects of social stress on corticosterone, in a manner that seemed more notable in bLRs. For bHRs, enrichment also caused greater aggression during a neutral social encounter and nominally during defeat, and decreased anxiety-like behavior. To explore the neurobiology underlying the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. Our findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations.

压力是影响心理健康状况的一个重要因素;个人应对或处理压力的方式决定了他们未来是否会受到负面影响。压力反应是由遗传、环境和生活经历相互作用而形成的。社会心理压力在青春期的影响尤为明显,而青春期正是情绪障碍发展的关键时期。在这项研究中,我们比较了两种成熟的、经过选择性繁殖的 Sprague Dawley 大鼠品系,即 "内化型 "低反应品系(bLR)和 "外化型 "高反应品系(bHR),以研究遗传气质和青春期环境如何影响未来对社会交往和社会心理压力的反应,以及这些压力反应的决定因素如何相互作用。雄性 bLR 和 bHR 大鼠在经历社交失败之前的青春期暴露于社交和环境强化中,然后对其社交互动和焦虑样行为进行评估。青春期的丰富环境使大鼠表现出更多的社会交往,以及名义上较少的社会回避、失败时较少的屈服和对社会压力对皮质酮影响的恢复力,这种方式似乎在 bLRs 中更为明显。对 bHRs 而言,富集也会导致它们在中性社交中和名义上在失败时表现出更强的攻击性,并减少焦虑样行为。为了探索焦虑表型 bLRs 发展社会适应能力的神经生物学基础,研究人员对海马和脑核这两个介导压力调节和社会行为的脑区进行了 RNA-seq。以前与压力、社会行为、攻击性和探索活动相关的基因组在这两个区域都有差异表达,尤其是对调节社会行为的基因组影响更大。我们的研究结果进一步证明,青春期强化训练可以作为一种预防性经历,抵御未来的压力。通过操纵环境来诱导通常焦虑的动物系的社会适应能力具有转化意义,因为它强调了针对基因脆弱的青少年群体采取干预策略的可行性。
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引用次数: 0
Effects of acute stress on reward processing: A comprehensive meta-analysis of rodent and human studies 急性应激对奖赏加工的影响:啮齿动物和人类研究的综合荟萃分析
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-24 DOI: 10.1016/j.ynstr.2024.100647
Martino Schettino , Valeria Tarmati , Paola Castellano , Valeria Gigli , Luca Carnevali , Simona Cabib , Cristina Ottaviani , Cristina Orsini

Stressors can initiate a cascade of central and peripheral changes that modulate mesocorticolimbic dopaminergic circuits and, ultimately, behavioral response to rewards. Driven by the absence of conclusive evidence on this topic and the Research Domain Criteria framework, random-effects meta-analyses were adopted to quantify the effects of acute stressors on reward responsiveness, valuation, and learning in rodent and human subjects.

In rodents, acute stress reduced reward responsiveness (g = −1.43) and valuation (g = −0.32), while amplifying reward learning (g = 1.17). In humans, acute stress had marginal effects on valuation (g = 0.25), without affecting responsiveness and learning. Moderation analyses suggest that acute stress neither has unitary effects on reward processing in rodents nor in humans and that the duration of the stressor and specificity of reward experience (i.e., food vs drugs) may produce qualitatively and quantitatively different behavioral endpoints.

Subgroup analyses failed to reduce heterogeneity, which, together with the presence of publication bias, pose caution on the conclusions that can be drawn and point to the need of guidelines for the conduction of future studies in the field.

压力可引发一系列中枢和外周变化,从而调节中皮质边缘多巴胺能回路,并最终影响对奖赏的行为反应。在啮齿类动物中,急性应激降低了奖赏反应性(g = -1.43 )和评价性(g = -0.32),同时扩大了奖赏学习(g = 1.17)。在人类中,急性应激对估价的影响微乎其微(g = 0.25),但不影响反应性和学习。调节分析表明,急性应激对啮齿类动物和人类的奖赏加工都没有单一的影响,应激持续时间和奖赏体验的特异性(即食物与药物)可能会产生不同质和量的行为终点。亚组分析未能减少异质性,再加上发表偏倚的存在,对可以得出的结论提出了警告,并指出需要为今后开展该领域的研究提供指导。
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引用次数: 0
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Neurobiology of Stress
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