Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2.
Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2.
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社会隔离诱发精神分裂症样行为，可能与 HINT1、NMDA 受体 1 和多巴胺受体 2 相关
DOI：
10.1097/wnr.0000000000000775
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发表时间：
2017-05-24
期刊：
影响因子：
1.7
通讯作者：
Gao CG
中科院分区：
文献类型：
--
作者：
Li BJ;Liu P;Chu Z;Shang Y;Huan MX;Dang YH;Gao CG
遗传因素和早期生活逆境在精神分裂症的病因学中起主要作用。我们以前的研究表明，社会隔离（SI）在出生后早期的发展导致了一些持久的异常行为和病理生理特征类似的核心症状的一些人类神经精神疾病的小鼠。谷氨酸和多巴胺假说与精神分裂症的发展密切相关。谷氨酸N-甲基-D-天冬氨酸受体和多巴胺受体之间的串扰与组氨酸三联体核苷酸结合蛋白1（HINT 1）相关，其与多种精神疾病相关。我们研究了SI对精神分裂症样行为的影响，并采用酶联免疫吸附试验研究了C57小鼠中N-甲基-D-天冬氨酸受体NR 1亚基HINT 1和多巴胺2型受体（D2 R）的表达水平。我们发现，SI导致了一系列精神分裂症相关的缺陷，如社会退缩，焦虑症，认知障碍和感觉运动门控障碍。这些异常表型包括HINT 1、NR 1和D2 R的改变。SI可以被认为是早期生活应激对小鼠精神分裂症相关行为影响的一个可靠模型。HINT 1、NR 1和D2 R之间的潜在相互作用可能是SI诱导的行为缺陷的基础。
Both genetic factors and early life adversity play major roles in the etiology of schizophrenia. Our previous studies indicated that social isolation (SI) during early postnatal development leads to several lasting abnormal behavioral and pathophysiological features resembling the core symptoms of some human neuropsychiatric disorders in mice. The glutamate and dopamine hypotheses are tightly linked to the development of schizophrenia. The cross-talk between glutamate N-methyl-D-aspartate acid receptors and dopamine receptors is associated with histidine triad nucleotide binding protein 1 (HINT1), which is correlated with diverse psychiatric disorders. We examined the effects of SI on schizophrenia-like behavior and used enzyme-linked immunosorbent assays to investigate the expression levels of HINT1, the NR1 subunit of N-methyl-D-aspartate acid receptor, and dopamine type 2 receptor (D2R) in C57 mice. We found that SI leads to a series of schizophrenia-related deficits, such as social withdrawal, anxiety disorder, cognitive impairments, and sensorimotor gating disturbances. These abnormal phenotypes paralleled changes of HINT1, NR1, and D2R. SI may be considered a robust model of the effects of early life stress on the schizophrenia-related behaviors in mice. Potential interactions among HINT1, NR1, and D2R may underlie the behavioral deficits induced by SI.