Fujiwara Tomonori, Sanada Masumi, Kofuji Takefumi, Akagawa Kimio
Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Radioisotope Laboratory, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
J Neurochem. 2016 Jul;138(1):117-23. doi: 10.1111/jnc.13634. Epub 2016 May 23.
HPC-1/syntaxin1A (STX1A), a neuronal soluble N-ethylmaleimide-sensitive fusion attachment protein receptor, contributes to neural function in the CNS by regulating transmitter release. Recent studies reported that STX1A is associated with human neuropsychological disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Previously, we showed that STX1A null mutant mice (STX1A KO) exhibit neuropsychological abnormalities, such as fear memory deficits, attenuation of latent inhibition, and unusual social behavior. These observations suggested that STX1A may be involved in the neuropsychological basis of these abnormalities. Here, to study the neural basis of social behavior, we analyzed the profile of unusual social behavior in STX1A KO with a social novelty preference test, which is a useful method for quantification of social behavior. Interestingly, the unusual social behavior in STX1A KO was partially rescued by intracerebroventricular administration of oxytocin (OXT). In vivo microdialysis studies revealed that the extracellular OXT concentration in the CNS of STX1A KO was significantly lower compared with wild-type mice. Furthermore, dopamine-induced OXT release was reduced in STX1A KO. These results suggested that STX1A plays an important role in social behavior through regulation of the OXTergic neural system. Dopamine (DA) release is reduced in CNS of syntaxin1A null mutant mice (STX1A KO). Unusual social behavior was observed in STX1A KO. We found that oxytocin (OXT) release, which was stimulated by DA, was reduced and was rescued the unusual social behavior in STX1A KO was rescued by OXT. These results indicated that STX1A plays an important role in promoting social behavior through regulation of DA-induced OXT release in amygdala.
HPC-1/ syntaxin1A（STX1A）是一种神经元可溶性N-乙基马来酰亚胺敏感融合附着蛋白受体，通过调节神经递质释放对中枢神经系统的神经功能发挥作用。最近的研究报道，STX1A与人类神经心理障碍有关，如自闭症谱系障碍和注意力缺陷多动障碍。此前，我们发现STX1A基因敲除小鼠（STX1A KO）表现出神经心理异常，如恐惧记忆缺陷、潜伏抑制减弱和异常的社交行为。这些观察结果表明，STX1A可能参与了这些异常的神经心理基础。在此，为了研究社交行为的神经基础，我们通过社交新奇偏好测试分析了STX1A KO小鼠异常社交行为的特征，这是一种量化社交行为的有用方法。有趣的是，通过脑室内注射催产素（OXT）可部分挽救STX1A KO小鼠的异常社交行为。体内微透析研究表明，与野生型小鼠相比，STX1A KO小鼠中枢神经系统中细胞外OXT浓度显著降低。此外，多巴胺诱导的OXT释放在STX1A KO小鼠中减少。这些结果表明，STX1A通过调节催产素能神经系统在社交行为中发挥重要作用。 syntaxin1A基因敲除小鼠（STX1A KO）中枢神经系统中的多巴胺（DA）释放减少。在STX1A KO小鼠中观察到异常社交行为。我们发现，由DA刺激的催产素（OXT）释放减少，而OXT挽救了STX1A KO小鼠的异常社交行为。这些结果表明，STX1A通过调节杏仁核中DA诱导的OXT释放，在促进社交行为中发挥重要作用。
