Minocycline alleviates behavioral deficits and inhibits microglial activation induced by intrahippocampal administration of Granulocyte-Macrophage Colony-Stimulating Factor in adult rats.
Some evidence has shown an increased number of activated microglial cells in patients with schizophrenia. It is hypothesized that activated microglia may contribute to the pathogenesis of schizophrenia. We injected saline or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) into the ventral hippocampus in adult Sprague-Dawley rats via micro-pump; at the same time, the rats were intragastrically administrated with saline or minocycline once a day for 14 consecutive days. Then, behavioral tests were examined and microglia were assessed using immunohistochemistry method. GM-CSF-injected group showed significant behavioral deficits (hyperlocomotion, social interaction deficits, prepulse inhibition (PPI) deficits). There was a dramatic increase of the number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared with those in saline-injected group in immunohistochemistry. Minocycline was able to ameliorate deficits of social interaction and PPI but not hyperlocomotion. Minocycline was also able to inhibit the microglial activation. In conclusion, intrahippocampal administration of GM-CSF in adult rats may serve as a potential schizophrenia animal model, which may be related with the microglia hypothesis of schizophrenia.
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.
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F
Zhu
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.
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Y
Liu
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.
J
J
Zhao
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.
Y
Y
Zheng
D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000187:drug effects*; D008911:Minocycline / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced*
D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D008911:Minocycline
Granulocyte–Macrophage Colony-Stimulating Factor; animal model; hippocampus; microglia hypothesis; schizophrenia