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A single low dose of valproic acid in late prenatal life alters postnatal behavior and glutamic acid decarboxylase levels in the mouse

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单位: [1]Shandong Acad Med Sci, Inst Basic Med, Jingshi Rd 18877, Jinan 250062, Shandong, Peoples R China [2]Univ Hong Kong, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China [3]Univ Hong Kong, State Key Lab Brain & Cognit Sci, Pokfulam, Hong Kong, Peoples R China [4]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Neurol,Hangzhou,Zhejiang,Peoples R China [5]Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Forens & Neurodev Sci, London, England
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关键词: Valproic acid Valproate Autism spectrum disorder ASD Mouse Glutamic acid decarboxylase

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Rationale: Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD). Many previous studies used relatively high doses of VPA during early pregnancy, potentially confounding interpretation because the offspring are the 'survivors' of a toxic insult. Low dose or late gestation exposure has not been widely studied. Objectives: We examined the behavioral sequelae of late gestation exposure to low dose VPA in the mouse. We also examined postnatal levels of glutamic acid decarboxylase (GAD65 and GAD67) as markers for GABA neurons, because GABA pathology and subsequent excitatory/inhibitory imbalance is strongly implicated in ASD. Methods: Pregnant C57BL/6N mice received a single subcutaneous injection of 100 or 200 mg/kg on gestation day 17. The control group received a saline injection on the same day. The offspring were tested in a battery of behavioral tests in adolescence and adulthood. Six brain regions were harvested and GAD65 and GAD67 were measured by western blotting. Results: Compared to saline-exposed controls, adult mice exposed to prenatal VPA had impaired novel object exploration and fear conditioning anomalies. GAD67 was decreased in midbrain, olfactory bulb, prefrontal cortex and increased in cerebellum, hippocampus and striatum; GAD65 was decreased in all 6 regions. Conclusions: Our results suggest that a low dose of VPA in late pregnancy has persistent effects on brain development, and in particular the GABA system, which may be relevant to ASD. Further attention to the impact of gestation time and dose of exposure in VPA-induced ASD models is encouraged. (C) 2016 Published by Elsevier B.V.

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出版当年[2015]版:
大类 | 3 区 医学
小类 | 3 区 行为科学 3 区 神经科学
最新[2025]版:
大类 | 3 区 心理学
小类 | 3 区 行为科学 4 区 神经科学
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出版当年[2014]版:
Q2 NEUROSCIENCES Q2 BEHAVIORAL SCIENCES
最新[2024]版:
Q2 BEHAVIORAL SCIENCES Q3 NEUROSCIENCES

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第一作者单位: [1]Shandong Acad Med Sci, Inst Basic Med, Jingshi Rd 18877, Jinan 250062, Shandong, Peoples R China [2]Univ Hong Kong, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China
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通讯机构: [1]Shandong Acad Med Sci, Inst Basic Med, Jingshi Rd 18877, Jinan 250062, Shandong, Peoples R China [2]Univ Hong Kong, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China
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