Causal role of unregulated mTOR signaling in autism-related behavioral deficits in mouse models of t

• 作 者: AtsushiSato[1]ShinyaKasai[2]ToshiyukiKobayashi[3]YukioTakamatsu[2]OkioHino[3]KazutakaIkeda[2]MasashiMizuguchi[4]
• 机 构: Addictive Substance Project,Tokyo Metropolitan Institute of Medical Science
• 出 处: 中华医学会第十一次全国精神医学学术会议暨第三届亚洲神经精神药理学术会议
• 发表日期: 2013年期

　　Objective Autism spectrum disorder (ASD) is a neurodevelopmental disorder that mainly affects reciprocal social interaction.Recent advances in ASD genetics have not necessarily led to its effective pharmacological therapies.A number of individuals with ASD have single-gene disorders such as tuberous sclerosis complex (TSC),caused by mutations in the TSC1 or TSC2 gene.TSC is one of the leading causes of syndromic ASD.Unregulated signaling by mammalian target of rapamycin (mTOR),the central pathomechanism of TSC,is considered as the cause and the therapeutic target of ASD in TSC.We previously reported the impairment in social interaction in Tsc1+/-and Tsc2+/-mice,mouse models of TSC,and the efficiency of the mTOR inhibitor rapamycin on the impairment.We investigated the causal role of unregulated mTOR signaling in the above deficits.We also compared the severity of social impairment in Tsc1+/-,Tsc2+/-,and Tsc1/Tsc2 double-heterozygous mice.