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Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques 长期饮酒会改变猕猴的性别依赖性 BNST 神经元功能
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-30 DOI: 10.1016/j.ynstr.2024.100638
Kristen E. Pleil , Kathleen A. Grant , Verginia C. Cuzon Carlson , Thomas L. Kash

Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder. We performed slice electrophysiology recordings from BNST neurons in male and female monkeys following daily “open access” (22 h/day) to 4% ethanol and water for more than one year or control conditions. We found that BNST neurons from control females had reduced overall current density, hyperpolarization-activated depolarizing current (Ih), and inward rectification, as well as higher membrane resistance and greater synaptic glutamatergic release and excitatory drive, than those from control males, suggesting that female BNST neurons are more basally excited than those from males. Chronic alcohol drinking produced a shift in these measures in both sexes, decreasing current density, Ih, and inward rectification and increasing synaptic excitation. In addition, network activity-dependent synaptic inhibition was basally higher in BNST neurons of males than females, and alcohol exposure increased this in both sexes, a putative homeostatic mechanism to counter hyperexcitability. Altogether, these results suggest that the rhesus BNST is more basally excited in females than males and chronic alcohol drinking produces an overall increase in excitability and synaptic excitation. These results shed light on the mechanisms contributing to the female-biased susceptibility to neuropsychiatric diseases including co-expressed anxiety and alcohol use disorder.

反复饮酒会导致多种神经精神疾病,包括酒精使用障碍以及共同表现的焦虑和情绪障碍。在与男性相同的酒精接触史下,女性更容易患上和表现出这些疾病,这表明她们可能对控制饮酒、压力反应和奖赏处理等行为的边缘脑区的酒精诱导可塑性更敏感。我们利用恒河猴饮酒转化模型,研究了纹状体末端床核(BNST)神经元的基础功能和可塑性的性别差异。我们对每天 "开放"(22 小时/天)接触 4% 乙醇和水超过一年的雄性和雌性猴子或对照组的 BNST 神经元进行了切片电生理学记录。我们发现,与对照组雄猴的神经元相比,对照组雌猴的 BNST 神经元的总体电流密度、超极化激活去极化电流(Ih)和内向整流都有所降低,膜电阻也更高,突触谷氨酸能释放和兴奋驱动力也更强,这表明雌猴的 BNST 神经元比雄猴的神经元基础兴奋性更高。长期饮酒会使男女神经元的这些指标发生变化,降低电流密度、Ih和内向整流,增加突触兴奋。此外,雄性 BNST 神经元的网络活动依赖性突触抑制在基础上高于雌性,而酒精暴露会增加这种抑制,这是一种抵消过度兴奋的假定同调机制。总之,这些结果表明,雌性恒河猴 BNST 的基础兴奋性高于雄性,而长期饮酒会导致兴奋性和突触兴奋的总体增加。这些结果揭示了导致雌性易患神经精神疾病(包括共同表现的焦虑症和酒精使用障碍)的机制。
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引用次数: 0
Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age 早期生活压力会损害恐惧记忆的获得和检索:性别效应、皮质酮调节,以及在青春期针对糖皮质激素受体的部分预防。
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-23 DOI: 10.1016/j.ynstr.2024.100636
Jeniffer Sanguino-Gómez, Harm J. Krugers

The early postnatal period is a sensitive time window that is characterized by several neurodevelopmental processes that define neuronal architecture and function later in life. Here, we examined in young adult mice, using an auditory fear conditioning paradigm, whether stress during the early postnatal period 1) impacts fear acquisition and memory consolidation in male and female mice; 2) alters the fear responsiveness to corticosterone and 3) whether effects of early-life stress (ELS) can be prevented by treating mice with a glucocorticoid (GR) antagonist at adolescence. Male and female mice were exposed to a limited nesting and bedding model of ELS from postnatal day (PND) 2–9 and injected i.p with RU38486 (RU486) at adolescent age (PND 28–30). At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. In conclusion, this study highlights the long-lasting consequences of early-life stress on fear memory processing and further illustrates 1) the potential of a glucocorticoid antagonist intervention during adolescence to mitigate these effects and 2) the partial modulation of the auditory retrieval upon post training administration of CORT, with all these effects being sex-dependent.

产后早期是一个敏感的时间窗口,其特点是有多个神经发育过程,这些过程决定了以后的神经元结构和功能。在这里,我们利用听觉恐惧条件反射范例研究了成年小鼠在出生后早期的应激是否会:1)影响雄性和雌性小鼠的恐惧获得和记忆巩固;2)改变对皮质酮的恐惧反应性;3)是否可以通过在青春期用糖皮质激素(GR)拮抗剂治疗小鼠来预防早期生活应激(ELS)的影响。雄性和雌性小鼠从出生后第2-9天开始暴露于有限的筑巢和铺垫的ELS模型中,并在青春期(第28-30天)肌注RU38486(RU486)。在小鼠两个月大时,对其进行恐惧条件反射(FC)范式训练(训练后给予或不给予皮质酮-CORT),并对恐惧获得过程中的冻结行为以及上下文和听觉记忆检索进行评分。我们观察到,ELS会特别损害雄性小鼠的恐惧获得能力,并降低雄性和雌性小鼠的情境记忆和听觉记忆检索能力。训练后急性服用 CORT 会增加雌性小鼠在听觉记忆检索过程中的冻结水平,但却会降低尤其是对照组雄性小鼠在音调呈现过程中的冻结水平。用 RU486 治疗可防止雄性小鼠在习得过程中的 ELS 效应,以及雌性小鼠在听觉记忆检索过程中的 ELS 效应。总之,这项研究强调了早期生活压力对恐惧记忆处理的长期影响,并进一步说明了:1)在青春期使用糖皮质激素拮抗剂干预有可能减轻这些影响;2)在训练后服用 CORT 可部分调节听觉检索,所有这些影响都与性别有关。
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引用次数: 0
Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study 在社交丰富的环境中,慢性不可预测压力的生理和行为传染/缓冲效应:初步研究
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-11 DOI: 10.1016/j.ynstr.2024.100635
Evren Eraslan , Magda J. Castelhano-Carlos , Liliana Amorim , Carina Soares-Cunha , Ana J. Rodrigues , Nuno Sousa

Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.

啮齿动物对同类的情绪状态很敏感。当有附属的社会伙伴存在时,应激反应的生理反应会减轻(缓冲),而应激个体的伙伴则会表现出行为和内分泌变化,这表明应激参数可以在群体成员之间传播(传染)。在这项研究中,我们以生活在 PhenoWorld(PhW)中的大鼠为研究对象,调查了它们在受到慢性压力后的行为和神经内分泌机制中的社会传染/缓冲现象。我们测试了三组大鼠(8 只应激大鼠、8 只非应激大鼠以及 4 和 4 的混合组),并在 4 种条件下对这些大鼠进行了分析:应激(纯应激组,n = 8)、非应激(天真对照组,n = 8)、来自混合组的应激(应激同伴组,n = 8)、来自混合组的非应激(非应激同伴组,n = 8)。 天真对照组动物不受干扰,而纯应激组动物则全部暴露于应激中。在混合处理条件下,半数动物受到应激(应激伴侣组),并与未受应激的伴侣同居(未受应激伴侣组)。我们证实了慢性不可预知应激(CUS)对生理、行为和神经内分泌终点的影响;体重增加、EPM中张开手臂的次数和时间以及杏仁核中催产素受体的表达水平因应激暴露而降低,而肾上腺重量则因应激而增加。此外,我们还发现,嬉戏、饲养和单独休息行为会因CUS而减少,而蜷缩行为会因CUS而增加。此外,我们还发现纯应激动物和应激伴侣动物之间体重增加和蜷缩行为的显著增加(应激缓冲),以及天真对照组和对照伴侣组之间情绪行为和催产素受体表达水平的显著应激传染效应。因此,我们证明在大鼠的生理参数、情绪行为和社会性笼养行为中存在明显的缓冲和传染效应,并认为催产素神经递质可能对这些效应起着中介作用。总之,本文的研究结果表明,生活在同一饲养环境中的动物的应激状态会影响群体行为。
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引用次数: 0
Acute stress differentially alters reward-related decision making and inhibitory control under threat of punishment 在惩罚威胁下,急性应激会不同程度地改变与奖赏相关的决策和抑制控制
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-05 DOI: 10.1016/j.ynstr.2024.100633
Giulio Laino Chiavegatti, Stan B. Floresco

Acute stress has various effects on cognition, executive function and certain forms of cost/benefit decision making. Recent studies in rodents indicate that acute stress differentially alters reward-related decisions involving particular types of costs and slows choice latencies. Yet, how stress alters decisions where rewards are linked to punishment is less clear. We examined how 1 h restraint stress, followed by behavioral testing 10 min later altered action-selection on two tasks involving reward-seeking under threat of punishment in well-trained male and female rats. One study used a risky decision-making task involving choice between a small/safe reward and a large/risky one that could coincide with shock, delivered with a probability that increased over blocks of trials. Stress increased risk aversion and punishment sensitivity, reducing preference for the larger/risky reward, while increasing decision latencies and trial omissions in both sexes, when rats were teste. A second study used a “behavioral control” task, requiring inhibition of approach towards a readily available reward associated with punishment. Here, food pellets were delivered over discrete trials, half of which coincided with a 12 s audiovisual cue, signalling that reward retrieval prior to cue termination would deliver shock. Stress exerted sex- and timing-dependent effects on inhibitory control. Males became more impulsive and received more shocks on the stress test, whereas females were unaffected on the stress test, and were actually less impulsive when tested 24 h later. None of the effects of restraint stress were recapitulated by systemic treatment with physiological doses of corticosterone. These findings suggest acute stress induces qualitatively distinct and sometimes sex-dependent effects on punished reward-seeking that are critically dependent on whether animals must either choose between different actions or withhold them to obtain rewards and avoid punishment.

急性应激会对认知、执行功能和某些形式的成本/收益决策产生各种影响。最近在啮齿动物身上进行的研究表明,急性应激会不同程度地改变涉及特定类型成本的奖励相关决策,并减慢选择潜伏期。然而,压力如何改变奖励与惩罚相关的决策却不太清楚。我们对训练有素的雄性和雌性大鼠进行了一项研究,考察了 1 小时的束缚应激和 10 分钟后的行为测试如何改变它们在两项任务中的行动选择,这两项任务都涉及在惩罚威胁下寻求奖励。其中一项研究使用了风险决策任务,该任务涉及在小额/安全奖励和大额/风险奖励之间做出选择。当大鼠接受试验时,压力增加了风险厌恶和惩罚敏感性,降低了对较大/危险奖励的偏好,同时增加了雌雄大鼠的决策延迟和试验遗漏。第二项研究使用了 "行为控制 "任务,要求抑制大鼠接近与惩罚相关的现成奖励。在这项任务中,食物颗粒是在不连续的试验中投放的,其中一半试验与 12 秒钟的视听提示相吻合,这表明在提示终止之前取回奖励将导致电击。应激对抑制控制产生了性别和时间上的影响。在压力测试中,雄性动物变得更冲动,受到的电击也更多,而雌性动物在压力测试中不受影响,而且在24小时后的测试中,雌性动物的冲动性实际上更低。用生理剂量的皮质酮进行全身治疗后,束缚应激的影响均未再现。这些研究结果表明,急性应激会对受惩罚的寻求奖赏行为产生质量上不同的、有时是性别依赖性的影响,这些影响主要取决于动物是否必须在不同的行为之间做出选择,或者必须暂停这些行为以获得奖赏和避免惩罚。
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引用次数: 0
Predator odor stress reactivity, alcohol drinking and the endocannabinoid system 捕食者气味应激反应、饮酒和内源性大麻素系统
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-04 DOI: 10.1016/j.ynstr.2024.100634
Laura C. Ornelas , Joyce Besheer

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and individual differences in response to stress suggest resilient and susceptible populations. Using animal models to target neurobiological mechanisms associated with individual variability in stress coping responses and the relationship with subsequent increases in alcohol consumption has important implications for the field of traumatic stress and alcohol disorders. The current review discusses the unique advantages of utilizing predator odor stressor exposure models, specifically using 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) on better understanding PTSD pathophysiology and neurobiological mechanisms associated with stress reactivity and subsequent increases in alcohol drinking. Furthermore, there has been increasing interest regarding the role of the endocannabinoid system in modulating behavioral responses to stress with an emphasis on stress coping and individual differences in stress-susceptibility. Therefore, the current review focuses on the topic of endocannabinoid modulation of stress reactive behaviors during and after exposure to a predator odor stressor, with implications on modulating distinctly different behavioral coping strategies.

创伤后应激障碍(PTSD)和酒精使用障碍(AUD)是高度并发症,对应激反应的个体差异表明有适应能力的人群和易受影响的人群。利用动物模型瞄准与压力应对反应个体差异相关的神经生物学机制以及与随后酒精消费增加的关系,对创伤应激障碍和酒精紊乱领域具有重要意义。本综述讨论了利用捕食者气味应激源暴露模型的独特优势,特别是利用 2,5-二氢-2,4,5-三甲基噻唑啉(TMT)来更好地了解创伤后应激障碍的病理生理学以及与应激反应性和随后的饮酒增加有关的神经生物学机制。此外,人们越来越关注内源性大麻素系统在调节应激行为反应中的作用,重点是应激应对和应激易感性的个体差异。因此,本综述将重点放在内源性大麻素对暴露于捕食者气味应激源期间和之后的应激反应行为的调节作用,以及对调节截然不同的行为应对策略的影响。
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引用次数: 0
Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress 自体促肾上腺皮质激素和溶血磷脂酸缺乏症对长期暴露于不可预测的轻度应激的小鼠抑郁样行为的影响
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-04 DOI: 10.1016/j.ynstr.2024.100632
Chao Wang , Ningyuan Li , Yuqi Feng , Siqi Sun , Jingtong Rong , Xin-hui Xie , Shuxian Xu , Zhongchun Liu

The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid (LPA) and autotaxin (ATX) in individuals experiencing depression. However, the exact significance of this phenomenon in relation to depression remains inconclusive. This study seeks to explore the deeper implications of these observations. We assessed alterations in ATX and LPA in both the control group and the chronic unpredictable mild stress (CUMS) model group. Additionally, the impact of ATX adeno-associated virus (AAV-ATX) injection into the hippocampus was validated through behavioral tests in CUMS-exposed mice. Furthermore, we probed the effects of LPA on synapse-associated proteins both in HT22 cells and within the mouse hippocampus. The mechanisms underpinning the LPA-triggered shifts in protein expression were further scrutinized. Hippocampal tissues were augmented with ATX to assess its potential to alleviate depression-like behavior by modulating synaptic-related proteins. Our findings suggest that the decrement in ATX and LPA levels alters the expression of proteins associated with synaptic plasticity in vitro and in vivo, such as synapsin-I (SYN), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Moreover, we discerned a role for the ERK/CREB signaling pathway in mediating the effects of ATX and LPA. Importantly, strategic supplementation of ATX effectively mitigated depression-like behaviors. This study indicates that the ATX-LPA pathway may influence depression-like behaviors by modulating synaptic plasticity in the brains of CUMS-exposed mice. These insights augment our understanding of depression's potential pathogenic mechanism in the context of lipid metabolism and propose promising therapeutic strategies for ameliorating the disease.

脂质参与抑郁症的机理引发了广泛的讨论。早期的研究发现,抑郁症患者体内溶血磷脂酸(LPA)和自体免疫球蛋白(ATX)的水平降低。然而,这一现象对抑郁症的确切意义仍无定论。本研究试图探索这些观察结果的深层含义。我们评估了对照组和慢性不可预测轻度应激(CUMS)模型组中 ATX 和 LPA 的变化。此外,我们还通过对暴露于 CUMS 的小鼠进行行为测试,验证了向海马注射 ATX 腺相关病毒(AAV-ATX)的影响。此外,我们还探究了LPA对HT22细胞和小鼠海马内突触相关蛋白的影响。我们还进一步研究了 LPA 触发蛋白质表达变化的机制。用 ATX 增强海马组织,以评估其通过调节突触相关蛋白来减轻抑郁样行为的潜力。我们的研究结果表明,ATX和LPA水平的降低会改变体外和体内与突触可塑性相关的蛋白质的表达,如突触素I(SYN)、突触素(SYP)和脑源性神经营养因子(BDNF)。此外,我们还发现ERK/CREB 信号通路在介导 ATX 和 LPA 的作用方面发挥了作用。重要的是,战略性地补充 ATX 能有效缓解抑郁样行为。这项研究表明,ATX-LPA通路可能通过调节CUMS暴露小鼠大脑的突触可塑性来影响抑郁样行为。这些见解加深了我们对脂质代谢背景下抑郁症潜在致病机制的理解,并为改善这种疾病提出了有前景的治疗策略。
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引用次数: 0
CRF binding protein activity in the hypothalamic paraventricular nucleus is essential for stress adaptations and normal maternal behaviour in lactating rats 下丘脑室旁核的 CRF 结合蛋白活性对哺乳期大鼠的应激适应和正常母性行为至关重要
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-27 DOI: 10.1016/j.ynstr.2024.100631
Alice Sanson , Paula Krieg , Milena M. Schramm , Kerstin Kellner , Rodrigue Maloumby , Stefanie M. Klampfl , Paula J. Brunton , Oliver J. Bosch

To ensure the unrestricted expression of maternal behaviour peripartum, activity of the corticotropin-releasing factor (CRF) system needs to be minimised. CRF binding protein (CRF-BP) might be crucial for this adaptation, as its primary function is to sequester freely available CRF and urocortin1, thereby dampening CRF receptor (CRF-R) signalling. So far, the role of CRF-BP in the maternal brain has barely been studied, and a potential role in curtailing activation of the stress axis is unknown.

We studied gene expression for CRF-BP and both CRF-R within the paraventricular nucleus (PVN) of the hypothalamus. In lactating rats, Crh-bp expression in the parvocellular PVN was significantly higher and Crh-r1 expression in the PVN significantly lower compared to virgin rats. Acute CRF-BP inhibition in the PVN with infusion of CRF(6–33) increased basal plasma corticosterone concentrations under unstressed conditions in dams. Furthermore, while acute intra-PVN infusion of CRF increased corticosterone secretion in virgin rats, it was ineffective in vehicle (VEH)-pre-treated lactating rats, probably due to a buffering effect of CRF-BP. Indeed, pre-treatment with CRF(6–33) reinstated a corticosterone response to CRF in lactating rats, highlighting the critical role of CRF-BP in maintaining attenuated stress reactivity in lactation. To our knowledge, this is the first study linking hypothalamic CRF-BP activity to hypothalamic-pituitary-adrenal axis regulation in lactation. In terms of behaviour, acute CRF-BP inhibition in the PVN under non-stress conditions reduced blanket nursing 60 min and licking/grooming 90 min after infusion compared to VEH-treated rats, while increasing maternal aggression towards an intruder. Lastly, chronic intra-PVN inhibition of CRF-BP strongly reduced maternal aggression, with modest effects on maternal motivation and care.

Taken together, intact activity of the CRF-BP in the PVN during the postpartum period is essential for the dampened responsiveness of the stress axis, as well as for the full expression of appropriate maternal behaviour.

为了确保围产期母性行为的不受限制表达,需要尽量减少促肾上腺皮质激素释放因子(CRF)系统的活动。CRF结合蛋白(CRF-BP)可能是这种适应的关键,因为它的主要功能是封闭可自由利用的CRF和尿皮质素1,从而抑制CRF受体(CRF-R)的信号传导。我们研究了下丘脑室旁核(PVN)中 CRF-BP 和 CRF-R 的基因表达。与原始大鼠相比,哺乳大鼠下丘脑室旁核(PVN)中Crh-bp的表达明显较高,而Crh-r1的表达则明显较低。通过输注 CRF(6-33)抑制 PVN 中的急性 CRF-BP,可增加母鼠在非应激条件下的基础血浆皮质酮浓度。此外,虽然在PVN内急性输注CRF可增加处女大鼠的皮质酮分泌,但对经车辆(VEH)预处理的泌乳大鼠却无效,这可能是由于CRF-BP的缓冲作用。事实上,CRF(6-33)的预处理恢复了哺乳期大鼠对CRF的皮质酮反应,突出了CRF-BP在维持哺乳期应激反应减弱中的关键作用。据我们所知,这是首次将哺乳期下丘脑 CRF-BP 活性与下丘脑-垂体-肾上腺轴调节联系起来的研究。在行为方面,与 VEH 处理的大鼠相比,非应激条件下 PVN 内的急性 CRF-BP 抑制减少了输注后 60 分钟的空白哺乳和 90 分钟的舔舐/梳理,同时增加了母体对入侵者的攻击性。总之,在产后期间,PVN 中 CRF-BP 的完整活性对于抑制应激轴的反应以及充分表达适当的母性行为至关重要。
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引用次数: 0
Emotional abuse mediated by negative automatic thoughts impacts functional connectivity during adolescence 以消极的自动想法为中介的情感虐待影响青春期的功能连通性
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-19 DOI: 10.1016/j.ynstr.2024.100623
Dageon Yeo , Seulgi Lee , Haemi Choi , Min-Hyeon Park , Bumhee Park

Background

Emotional abuse during childhood and adolescence is thought to be associated with the brain; however, the neural mechanism underlying the cognitive process remains unknown. Therefore, we aimed to investigate the mediating effect of negative automatic thoughts on the relationship between emotional abuse and resting-state functional connectivity (rsFC) during adolescence.

Method

Our community sample included 54 adolescents aged 13–17 years in the statistical analysis. Resting-state functional and structural magnetic resonance imaging (MRI) was performed, while emotional abuse and negative automatic thoughts were assessed using self-reported scales. A mediation analysis was used to assess the contributions of early traumatic events and negative automatic thoughts to resting functional connectivity.

Result

Higher negative automatic thoughts were associated with lower connectivity in the context of greater emotional abuse (i.e., suppression effect). Thus, the relationships between emotional abuse and connectivity in the precuneus (pCun)-medial prefrontal cortex, parahippocampal cortex-extrastriate cortex, and temporal cortex-temporal pole were decreased by negative automatic thoughts. In contrast, functional connections in the pCun-pCun, pCun-precuneus/posterior cingulate cortex, and nucleus accumbens-somatomotor areas were strongly mediated when emotionally abused adolescents reported a high tendency for negative automatic thoughts.

Conclusion

Negative automatic thoughts strengthened the relationship between emotional abuse and rsFC. These findings highlight the underlying cognitive processing of the traumatic event-neural system, supporting the use of cognitive therapy for post-traumatic symptoms.

背景人们认为童年和青少年时期的情感虐待与大脑有关;然而,这一认知过程的神经机制仍然未知。因此,我们旨在研究消极自动想法对青春期情感虐待与静息态功能连通性(rsFC)之间关系的中介作用。我们对54名13-17岁的青少年进行了社区样本统计分析,并进行了静息状态功能和结构磁共振成像(MRI)检查,同时使用自我报告量表对情感虐待和消极自动想法进行了评估。结果较高的消极自动想法与较低的连接性有关,而较高的情绪虐待程度则与较低的连接性有关(即抑制效应)。因此,情绪虐待与楔前皮层(pCun)-内侧前额叶皮层、海马旁皮层-外显皮层和颞皮层-颞极的连接性之间的关系因消极自动想法而降低。与此相反,当遭受情感虐待的青少年报告其有较高的消极自动想法倾向时,pCun-pCun、pCun-precuneus/后扣带回皮层和伏隔核-躯体运动区的功能连接则会受到强烈的介导。这些发现强调了创伤事件-神经系统的潜在认知处理过程,支持使用认知疗法治疗创伤后症状。
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引用次数: 0
A gut (microbiome) feeling about addiction: Interactions with stress and social systems 特约评论--"压力与酒精 "特刊:关于成瘾的直觉(微生物组)感受:与压力和社会系统的相互作用
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-18 DOI: 10.1016/j.ynstr.2024.100629
Rubén García-Cabrerizo , John F. Cryan

In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.

近年来,人们越来越关注居住在我们肠道中的微生物之间错综复杂、多种多样的联系,以及它们对大脑健康和中枢神经系统疾病的影响。人们已经转变了观念,认识到吸毒上瘾不仅仅是一种影响大脑的疾病,它现在被认为是一种疾病,还涉及肠道微生物群等外部因素,这些因素可能会影响易感性和成瘾行为的发展。此外,与肠道微生物群密切相关的压力和社会互动也是成瘾的强大调节因素。这篇综述深入探讨了微生物群-压力-免疫轴可能影响药物成瘾和社会行为的机制。这项工作综合了临床前和临床证据,证明了压力、社会行为、药物使用障碍和肠道微生物群之间的双向交流,表明肠道微生物可能调节社会压力,对药物成瘾具有重要意义。
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引用次数: 0
β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction 灵长类背外侧前额叶皮层 GABA 能中间神经元上的β1-肾上腺素受体表达:在压力诱导的认知功能障碍中的潜在作用
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-15 DOI: 10.1016/j.ynstr.2024.100628
M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten

Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) “Delay cells”, involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC. We found β1-AR robustly expressed on different classes of inhibitory neurons labeled by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Immunoelectron microscopy confirmed β1-AR expression on the plasma membrane of PV-expressing dendrites. PV interneurons can be identified as fast-spiking (FS) in physiological recordings, and thus were studied in macaques performing a working memory task. Iontophoresis of a β1-AR agonist had a mixed effect, increasing the firing of a subset and decreasing the firing of others, likely reflecting loss of firing of the entire microcircuit. This loss of overall firing likely contributes to impaired working memory during stress, as pretreatment with the selective β1-AR antagonist, nebivolol, prevented stress-induced working memory deficits. Thus, selective β1-AR antagonists may be helpful in treating stress-related disorders.

无法控制的压力会损害工作记忆,并降低背外侧前额叶皮层(dlPFC)"延迟细胞 "的发射,这涉及到高水平的去甲肾上腺素和多巴胺释放。以前的研究主要关注儿茶酚胺对前额叶皮质锥体细胞的作用,但抑制性中间神经元也可能起作用。本研究将免疫组化、多尺度显微镜、离子渗透生理学和行为分析结合起来,研究了β1-去甲肾上腺素能受体(β1-ARs)对第III层dlPFC抑制性神经元的影响。我们发现β1-AR在不同类别的抑制性神经元上都有很强的表达,这些抑制性神经元由钙结合蛋白钙宾蛋白(CB)、钙视蛋白(CR)和钙旁蛋白(PV)标记。免疫电镜证实,β1-AR 在 PV 表达树突的质膜上表达。在生理记录中,PV 中间神经元可被识别为快速尖峰(FS),因此在猕猴执行工作记忆任务时对其进行了研究。对β1-AR激动剂进行离子注入会产生混合效应,增加一个子集的点燃,减少其他子集的点燃,这可能反映了整个微电路点燃的丧失。这种整体发射损失可能是应激时工作记忆受损的原因之一,因为使用选择性β1-AR拮抗剂奈必洛尔进行预处理可防止应激引起的工作记忆缺陷。因此,选择性β1-AR拮抗剂可能有助于治疗应激相关疾病。
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引用次数: 0
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Neurobiology of Stress
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