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催产素可改善自闭症小鼠的社交行为

2015年01月22日 浏览量: 评论(0) 来源:Science Translational Medicine 作者:O. Peñagarikano 责任编辑:cxyinfo2014
摘要:催产素是一种帮助动物建立社会关系和信任的激素;人们对将它作为一种可能的对自闭症谱系障碍的治疗产生了强烈兴趣,但临床试验迄今产生的是混杂的结果。Olga Peñagarikano和同事在一个自闭症小鼠模型中证明,催产素可明显地改善其社会行为,如果进行早期治疗,这一裨益可能长时间持续。

Olga Peñagarikano和同事在一个自闭症小鼠模型中证明,催产素可明显地改善其社会行为,如果进行早期治疗,这一裨益可能长时间持续。

催产素是一种帮助动物建立社会关系和信任的激素;人们对将它作为一种可能的对自闭症谱系障碍的治疗产生了强烈兴趣,但临床试验迄今产生的是混杂的结果。

为了了解该激素如何在大脑中作用,研究人员通过删除一个基因而创制了一种患遗传型自闭症的小鼠,它会引起包括自闭症谱系障碍的遗传性发育综合症。他们发现,接受催产素治疗的自闭症小鼠在行为测试上的表现会好得多,它们会比单独小鼠花更多时间与其它小鼠互动。给这些小鼠一种可在脑中激发催产素释放的药物会产生相同的效果。解剖发现,患自闭症小鼠的脑子显示该激素水平较低,这是因为产生催产素的神经元较少所致。

为了测试催产素是否能在神经元回路还在形成中的早期发育时期影响这些小鼠,Peñagarikano和同事在它们出生后不久每日用催产素治疗这些自闭症小鼠。早期治疗可对小鼠的社交技能产生持久的裨益,它能在停止治疗后持续一周以上。

这些结果支持对催产素作为可能治疗某些形式的自闭症进行探索,并提示可能有一个关键的时间窗,在该时间窗内,早期治疗可帮助恢复社交能力。

原文链接:Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior inCntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit.

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