Male‐specific alteration in excitatory post‐synaptic development and social interaction in pre‐natal valproic acid exposure model of autism spectrum disorder

作者：Ki Chan Kim, Pitna Kim, Hyo Sang Go, Chang Soon Choi, Jin Hee Park, Hee Jin Kim, Se Jin Jeon, Ike Campomayor dela Peña, Seol‐Heui Han, Jae Hoon Cheong, Jong Hoon Ryu, Chan Young Shin · 发表于：Journal of Neurochemistry · 年份：2013 · DOI：10.1111/jnc.12147 · 被引用次数：214 · 研究领域：Autism Spectrum Disorder Research、Genetics and Neurodevelopmental Disorders、Child Development and Digital Technology

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by three main behavioral symptoms including social deficits, impaired communication, and stereotyped and repetitive behaviors. ASD prevalence shows gender bias to male. Prenatal exposure to valproic acid (VPA), a drug used in epilepsy and bipolar disorder, induces autistic symptoms in both human and rodents. As we reported previously, prenatally VPA-exposed animals at E12 showed impairment in social behavior without any overt reproductive toxicity. Social interactions were not significantly different between male and female rats in control condition. However, VPA-exposed male offspring showed significantly impaired social interaction while female offspring showed only marginal deficits in social interaction. Similar male inclination was observed in hyperactivity behavior induced by VPA. In addition to the ASD-like behavioral phenotype, prenatally VPA-exposed rat offspring shows crooked tail phenotype, which was not different between male and female groups. Both male and female rat showed reduced GABAergic neuronal marker GAD and increased glutamatergic neuronal marker vGluT1 expression. Interestingly, despite of the similar increased expression of vGluT1, post-synaptic marker proteins such as PSD-95 and α-CAMKII expression was significantly elevated only in male offspring. Electron microscopy showed increased number of post-synapse in male but not in female at 4 weeks of age. These results migh...