Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression.
Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression.
复制标题
神经类固醇减少了社会隔离引起的行为缺陷：与神经类固醇介导的BDNF表达上调的拟议联系。
DOI：
10.3389/fendo.2011.00073
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发表时间：
2011
影响因子：
5.2
通讯作者：
Pinna G
中科院分区：
文献类型：
--
作者：
Nin MS;Martinez LA;Pibiri F;Nelson M;Pinna G
选择性5-羟色胺再摄取抑制剂抗抑郁药的药理作用可能包括使脑内脑源性神经营养因子(BDNF)和神经类固醇(如孕酮代谢物别孕酮)水平的正常化，抑郁症和创伤后应激障碍(PTSD)患者的脑源性神经营养因子和神经类固醇水平降低。创伤后应激障碍和抑郁患者的别孕酮和脑源性神经营养因子水平降低与行为症状严重程度相关。抗抑郁治疗上调了别孕酮水平和BDNF的表达，与症状的改善显著相关，这表明神经类固醇的生物合成和BDNF的表达可能是相互关联的。使用社交隔离的小鼠作为行为缺陷的动物模型的临床前研究表明，氟西汀及其衍生物通过提高皮质边缘别孕酮和脑源性神经营养因子的mRNA表达水平，改善了焦虑样行为、恐惧反应和攻击行为。这些作用似乎是独立的，比这些药物对5-羟色胺再摄取抑制的作用更具选择性。因此，这篇综述提出的假设是，在创伤后应激障碍或抑郁症患者中，脑内别孕酮水平和BDNF表达上调可能是抗抑郁药或其他选择性脑类固醇激素刺激分子的有益作用至少部分参与的机制。
The pharmacological action of selective serotonin reuptake inhibitor antidepressants may include a normalization of the decreased brain levels of the brain-derived neurotrophic factor (BDNF) and of neurosteroids such as the progesterone metabolite allopregnanolone, which are decreased in patients with depression and posttraumatic stress disorders (PTSD). The allopregnanolone and BDNF level decrease in PTSD and depressed patients is associated with behavioral symptom severity. Antidepressant treatment upregulates both allopregnanolone levels and the expression of BDNF in a manner that significantly correlates with improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF expression may be interrelated. Preclinical studies using the socially isolated mouse as an animal model of behavioral deficits, which resemble some of the symptoms observed in PTSD patients, have shown that fluoxetine and derivatives improve anxiety-like behavior, fear responses and aggressive behavior by elevating the corticolimbic levels of allopregnanolone and BDNF mRNA expression. These actions appeared to be independent and more selective than the action of these drugs on serotonin reuptake inhibition. Hence, this review addresses the hypothesis that in PTSD or depressed patients, brain allopregnanolone levels, and BDNF expression upregulation may be mechanisms at least partially involved in the beneficial actions of antidepressants or other selective brain steroidogenic stimulant molecules.