Sun Lan, Min Li, Zhou Hao, Li Man, Shao Feng, Wang Weiwen
School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, 100871, China.
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Behav Brain Res. 2017 Aug 30;333:258-266. doi: 10.1016/j.bbr.2017.07.011. Epub 2017 Jul 10.
Social isolation is regarded as a cause of schizophrenia spectrum disorders. Animal models of schizophrenia are constructed by repeated early environment deprivation as an important paradigm to reveal its pathological mechanism. Male Sprague Dawley rats were assigned to either social-rearing (SR) or isolated-rearing (IR) groups during postnatal days (PNDs) 21-34. On PND 56, all rats underwent behavioral testing including locomotor activity, anxiety-related behaviors in an open field and prepulse inhibition (PPI). Then, the rats were sacrificed and prefrontal cortex (PFC) tissues were separated for high-throughput proteomics analysis and Western blot validation. Rats of the IR group showed increased spontaneous locomotion, increased anxiety-like behavior and disrupted PPI compared with rats of the SR group. Based on proteomics analysis, a total of 124 PFC proteins were found to be significantly differentially expressed between the SR group and the IR group, the most remarkable of which were glial fibrillary acidic protein (GFAP), Annexin A2 (ANXA2) and vimentin (VIM), three astrocyte biomarkers. Further Western blot measurement confirmed that the levels of GFAP, ANXA2 and VIM were increased significantly in IR rats. Adolescent social isolation induced schizophrenia-like behaviors and significantly different expression of 124 PFC proteins in adult rats, especially GFAP, ANXA2 and VIM, which suggests that astrocyte development might be involved in the neural mechanism of schizophrenia.
社会隔离被视为精神分裂症谱系障碍的一个病因。通过反复早期环境剥夺构建精神分裂症动物模型，作为揭示其病理机制的重要范式。将雄性斯普拉格-道利大鼠在出生后第21至34天分配到群居饲养（SR）组或隔离饲养（IR）组。在出生后第56天，所有大鼠接受行为测试，包括运动活动、旷场试验中的焦虑相关行为和前脉冲抑制（PPI）。然后，处死大鼠并分离前额叶皮质（PFC）组织用于高通量蛋白质组学分析和蛋白质印迹验证。与SR组大鼠相比，IR组大鼠表现出自发性运动增加、焦虑样行为增加和PPI破坏。基于蛋白质组学分析，发现SR组和IR组之间共有124种PFC蛋白存在显著差异表达，其中最显著的是胶质纤维酸性蛋白（GFAP）、膜联蛋白A2（ANXA2）和波形蛋白（VIM），这三种是星形胶质细胞生物标志物。进一步的蛋白质印迹测量证实，IR大鼠中GFAP、ANXA2和VIM的水平显著升高。青少年社会隔离诱导成年大鼠出现精神分裂症样行为和124种PFC蛋白的显著差异表达，尤其是GFAP、ANXA2和VIM，这表明星形胶质细胞发育可能参与了精神分裂症的神经机制。
