Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 333, Issue -, Pages 258-266Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2017.07.011
Keywords
Schizophrenia; Adolescent social isolation; PPI; Prefrontal cortex; Proteomic analysis; Astrocyte development
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Funding
- National Natural Science Foundation of China [31470988, 81471122]
- Beijing Key Laboratory of Behavior and Mental Health, the Chinese Academy of Sciences [KJZD-EW-L04]
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences
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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.
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