Long-lasting Behavioral and Neuroanatomical Effects of Postnatal Valproic Acid Treatment.
Long-lasting Behavioral and Neuroanatomical Effects of Postnatal Valproic Acid Treatment.
复制标题
产后丙戊酸治疗的长期行为和神经解剖学影响。
DOI：
10.1016/j.neuroscience.2020.02.029
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发表时间：
2020
期刊：
影响因子：
3.3
通讯作者：
Kusnecov,AlexanderW
中科院分区：
文献类型：
--
作者：
Norton,SaraA;Gifford,JanaceJ;Pawlak,AnthonyP;Derbaly,Anna;Sherman,SaraL;Zhang,Huaye;Wagner,GeorgeC;Kusnecov,AlexanderW
在出生后早期给予小鼠丙戊酸（VPA）可导致与在自闭症谱系障碍（ASD）患者中观察到的相似的社交、认知和运动缺陷。然而，以前关于早期暴露于VPA的影响的研究主要集中在生命的青少年时期之前或期间发生的行为缺陷。鉴于ASD是一种终身疾病，本研究应该扩展我们对出生后早期VPA至成年后行为特征的理解。在出生后第14天（P14）接受VPA治疗的雄性小鼠表现出攻击性增加，高架十字迷宫中对开放臂的回避减少，Y迷宫中的逆转学习受损。这可能表明在出生后第二周接受VPA处理的雄性（而非雌性）小鼠中存在抑制解除或冲动表型。VPA处理小鼠mPFC中树突棘密度降低和树突棘形态异常可能表明PFC功能减退，与观察到的行为差异一致。由于这些类型的长期缺陷并非仅见于ASD，因此生命早期暴露于VPA可能反映了几种发育障碍（包括ASD、ADHD和行为障碍）常见的神经生物学领域的功能障碍。
Valproic acid (VPA) administered to mice during the early postnatal period causes social, cognitive, and motor deficits similar to those observed in humans with autism spectrum disorder (ASD). However, previous studies on the effects of early exposure to VPA have largely focused on behavioral deficits occurring before or during the juvenile period of life. Given that ASD is a life-long condition, the present study ought to extend our understanding of the behavioral profile following early postnatal VPA into adulthood. Male mice treated with VPA on postnatal day 14 (P14) displayed increased aggression, decreased avoidance of the open arms in the elevated plus maze, and impaired reversal learning in the Y maze. This may indicate a disinhibited or impulsive phenotype in male, but not female, mice treated with VPA during the second week of postnatal life. Decreased dendritic spine density and dendritic spine morphological abnormalities in the mPFC of VPA-treated mice may be indicative of PFC hypofunction, consistent with the observed behavioral differences. Since these types of long-lasting deficits are not exclusively found in ASD, early life exposure to VPA may reflect dysfunction of a neurobiological domain common to several developmental disorders, including ASD, ADHD, and conduct disorder.