Antidepressant activities of escitalopram and blonanserin on prenatal and adolescent combined stress-induced depression model: Possible role of neurotrophic mechanism change in serum and nucleus accumbens.
Antidepressant activities of escitalopram and blonanserin on prenatal and adolescent combined stress-induced depression model: Possible role of neurotrophic mechanism change in serum and nucleus accumbens.
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DOI：
10.1016/j.jad.2019.01.007
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发表时间：
2019-03
影响因子：
6.6
通讯作者：
Kengo Furuse;W. Ukai;E. Hashimoto;Hanako Hashiguchi;Yoshiyasu Kigawa;T. Ishii;Masaya Tayama;Kenta Deriha;Masaki Shiraishi;C. Kawanishi
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文献类型：
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作者：
Kengo Furuse;W. Ukai;E. Hashimoto;Hanako Hashiguchi;Yoshiyasu Kigawa;T. Ishii;Masaya Tayama;Kenta Deriha;Masaki Shiraishi;C. Kawanishi
背景已有大量研究表明，生命早期的逆境经历与随后的大脑发育相关，然而，神经生物学机制赋予精神疾病发作的风险仍不清楚。我们给青春期大鼠服用皮质酮（CORT），无论是否在产前暴露于乙醇，然后服用抗抑郁药或抗精神病药，并检查抑郁和社会功能行为以及脑功能的改变。衍生的神经营养因子（BDNF）的水平在血清中，海马，前扣带皮层，和nucleus abbens.ResultsThe产前乙醇和青春期CORT的联合应激暴露延长不动时间在强迫游泳测试（FST），并增加调查次数和社会互动测试（SIT）的数量。艾司西酞普兰治疗逆转了抑郁样行为，伴随着血清和脑桥核中BDNF水平的降低，而布南色林治疗改善了异常的社会交往行为，降低了血清BDNF水平。关于难治性抑郁症和抗抑郁药/抗精神病药物治疗引起血清和脑局部BDNF水平的变化。结论这些结果强烈暗示在早期生活联合应激的病理生理学和治疗中血清和脑桥核BDNF水平的变化。诱发抑郁症，并强调艾司西酞普兰和新一代抗精神病药物布南色林对难治性抑郁症的治疗潜力。
AbstractBackgroundThere has been number of studies suggesting experiences of adversity in early life interrelated subsequent brain development, however, neurobiological mechanisms confer risk for onset of psychiatric illness remains unclear.MethodsIn order to elucidate the pathogenic mechanisms underlying early life adversity-induced refractory depression in more detail, we administered corticosterone (CORT) to adolescent rats with or without prenatal ethanol exposure followed by an antidepressant or antipsychotic and examined alterations in depressive and social function behaviors and brain-derived neurotrophic factor (BDNF) levels in serum, the hippocampus, anterior cingulate cortex, and nucleus accumbens.ResultsThe combined stress exposure of prenatal ethanol and adolescent CORT prolonged immobility times in the forced swim test (FST), and increased investigation times and numbers in the social interaction test (SIT). A treatment with escitalopram reversed depression-like behavior accompanied by reductions in BDNF levels in serum and the nucleus accumbens, while a treatment with blonanserin ameliorated abnormal social interaction behavior with reductions in serum BDNF levels.LimitationsFurther studies are needed to clarify the clinical evinces responding to these results, and many questions remain regarding the mechanisms by which refractory depression and antidepressant/antipsychotic treatments cause changes in serum and brain regional BDNF levels.ConclusionThese results strongly implicate changes in BDNF levels in serum and the nucleus accumbens in the pathophysiology and treatment of early life combined stress-induced depression and highlight the therapeutic potential of escitalopram and new generation antipsychotic blonanserin for treatment-resistant refractory depression.