Hippocampal BDNF overexpression or microR124a silencing reduces anxiety- and autism-like behaviors in rats
Hippocampal BDNF overexpression or microR124a silencing reduces anxiety- and autism-like behaviors in rats
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DOI：
10.1016/j.bbr.2017.03.010
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发表时间：
2017-05-30
影响因子：
2.7
通讯作者：
Bahi, Amine
中科院分区：
文献类型：
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作者：
Bahi, Amine
microRNA124a（miR124a）最近成为多种神经精神疾病的关键参与者，包括抑郁症，焦虑症，酗酒和可卡因成瘾。虽然我们以前报道过miR124a及其靶点脑源性神经营养因子（BDNF）在自闭症样行为中起重要作用，但其分子和行为功能障碍仍不清楚。本研究的目的是了解齿状回（DG）中miR124 a的持续减少和BDNF的增加对新生隔离诱导的焦虑和自闭症样行为的影响。在这里，我们报告说，慢病毒介导的沉默miR124a在成年DG衰减新生儿隔离诱导的焦虑样行为，在高架十字迷宫（ESTA）和开放领域（OF）的测试。此外，miR124a沉默降低了大理石掩埋测试（MBT），自我梳理（SG）和社会互动测试中的自闭症样表型。Pearson相关性表明，高水平的BDNF（miR124 a的直接靶点）与miR124 a表达呈负相关。有趣的是，DG中病毒介导的BDNF过表达也逆转了新生儿隔离诱导的焦虑和自闭症样表型。总的来说，这些发现表明miR124a通过其靶向BDNF可能影响新生儿隔离诱导的焦虑和自闭症样行为。总之，这些结果确实支持这样的假设，即离散海马区的miR124 a有助于焦虑和自闭症样行为，并可能参与自闭症谱系障碍作为一种持续和持久的条件发展的神经适应，因此为理解这种精神疾病的生理病理学提供了一个更清晰的机制框架。(C)2017爱思唯尔B.V.保留所有权利。
MicroRNA124a (miR124a) has emerged recently as a key player for multiple neuropsychiatric disorders including depression, anxiety, alcoholism, and cocaine addiction. Although we have previously reported that miR124a and its target the brain-derived neutrophic factor (BDNF) play an important role in autism-like behaviors, the molecular and behavioral dysfunctions remain unknown. The aim of this study was to understand the effects of sustained decreases in miR124a and increases of BDNF in the dentate gyrus (DG) on neonatal isolation-induced anxiety-and autism like behaviors in rats. Here we report that lentiviral-mediated silencing of miR124a in the adult DG attenuated neonatal isolation-induced anxiety-like behavior in the elevated plus maze (EPM) and open-field (OF) tests. Also, miR124a silencing decreased autism-like phenotype in the marble burying test (MBT), self-grooming (SG), and social interaction tests. Pearson's correlations demonstrated that high levels of BDNF, a direct target of miR124a, were negatively correlated with miR124a expression. Interestingly, viral-mediated BDNF overexpression in the DG also reversed the neonatal isolation-induced anxiety-and autism like phenotypes. Collectively, these findings suggest that miR124a, through its target BDNF, may influence neonatal isolation-induced anxiety-and autism like behaviors. In conclusion, these results do support the hypothesis that miR124a in discrete hippocampal areas contributes to anxiety- and autism-like behaviors and may be involved in the neuroadaptations underlying the development of autism spectrum disorders as a persistent and lasting condition, and therefore provide a clearer mechanistic framework for understanding the physiopathology of such psychiatric illnesses. (C) 2017 Elsevier B.V. All rights reserved.