title: Neonatal intrahippocampal injection of lipopolysaccharide induces deficits in social behavior and prepulse inhibition and microglial activation in rats: Implication for a new schizophrenia animal model.
abstract: Several lines of evidence have suggested that the dysregulation of immune system is involved in the pathogenesis of schizophrenia. Microglia are the resident macrophage of the brain and the major player in innate immunity in the brain. We hypothesized that microglia activation may be closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (PD7), and they were separately treated with saline or minocycline for consecutive 3days. Behavioral changes (locomotor activity, social interaction and prepulse inhibition) were examined in adulthood, and the number of microglia was assessed using immunohistochemistry at PD9, PD21 and PD67. The adult rats in LPS-injected group showed obvious behavioral alterations (deficits in social behavior and prepulse inhibition) and a persistently dramatic increase of number of activated microglial cells in the hippocampus, cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, pretreatment with minocycline could significantly rescue the behavioral deficits and prevent microglia activation. Our results suggest that neonatal intrahippocampal LPS injection may serve as a potential schizophrenia animal model, and inhibition of microglia activation may be a potential treatment strategy for schizophrenia.
authors: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan 410011, China.
authors: Furong
authors: F
authors: Zhu
authors: Brain Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510370, China.
authors: Lulu
authors: L
authors: Zhang
authors: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan 410011, China.
authors: Yu-qiang
authors: YQ
authors: Ding
authors: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan 410011, China. Electronic address: zhaojingpingcsu@163.com.
authors: Jingping
authors: J
authors: Zhao
authors: Mental Health Institute of The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan 410011, China; Brain Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510370, China.
authors: Yingjun
authors: Y
authors: Zheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D007267:Injections; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D065808:Prepulse Inhibition / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*; D012919:Social Behavior
chemical_list: D008070:Lipopolysaccharides
keywords: Animal model; Lipopolysaccharide; Microglia; Schizophrenia