Why may allopregnanolone help alleviate loneliness?
Why may allopregnanolone help alleviate loneliness?
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DOI：
10.1016/j.mehy.2015.09.004
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发表时间：
2015-12-01
影响因子：
4.7
通讯作者：
Cacioppo, J. T.
中科院分区：
文献类型：
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作者：
Cacioppo, S.;Cacioppo, J. T.
异孕烷醇酮（ALLO）是一种大脑内源性神经类固醇，其生物合成受损与许多行为功能障碍有关，这些行为功能障碍包括焦虑和抑郁样行为、攻击行为以及对情境恐惧条件反射的反应变化。最近的动物研究也证明了ALLO在社会隔离中的关键作用。虽然感知到的社会隔离可能有人类独有的方面，但也有跨物种的连续性。人类和动物的研究都表明，感知到的社会隔离（可以在动物和人类的行为中定义）对身体健康有不利影响，例如下丘脑垂体肾上腺（HPA）活性增加，脑源性神经营养因子（BDNF）表达减少，抑郁行为增加。动物和人类研究之间的相似性表明，感知到的社会隔离（孤独）也可能与ALLO合成的减少有关，这可能是通过海马、杏仁核和终纹床核（BNST）减少BDNF调节和增加HPA活性，特别是在社会威胁处理过程中。因此，人类外源性ALLO（或ALLO前体，如孕烯醇酮）可能有助于减轻孤独感。与我们的假设一致，在人类中外源性给予ALLO（或ALLO前体）已被证明可以改善各种与压力相关的疾病，这些疾病显示出动物和人类之间的相似性，即创伤后应激障碍，创伤性脑损伤。因为越来越多的证据表明ALLO对社会孤立的动物有好处，我们相信我们的ALLO假设也可以应用于人类的孤独。(C) 2015 Elsevier Ltd.版权所有。
Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well. (C) 2015 Elsevier Ltd. All rights reserved.