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 |
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| Affiliation: | 1. Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo (USP), São Paulo, Brazil;2. Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, Binghamton, NY 13902-6000, United States;1. Pediatrics and Neuroscience, Harvard Medical School, Lurie Center for Autism, Massachusetts General Hospital for Children, Boston, MA 02126, United States;2. Psychology and Neuroscience, Duke University, Durham, NC 27708, United States;3. Pediatrics and Anatomy/Neurobiology, University of California-Irvine, Irvine, CA 92697, United States;1. Preclinical Neurobiology Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;2. School of Psychology, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia;3. Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308, Australia;4. Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia;5. Schizophrenia Research Institute, Sydney, NSW, Australia |
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| 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 3 days. 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. |
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| Keywords: | Lipopolysaccharide Microglia Animal model Schizophrenia |
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