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
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引用次数: 0

摘要

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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Elevated GABAergic neurotransmission prevents chronic intermittent ethanol induced hyperexcitability of intrinsic and extrinsic inputs to the ventral subiculum of female rats

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.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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