Minocycline improves recognition memory and attenuates microglial activation in Gunn rat: A possible hyperbilirubinemia-induced animal model of schizophrenia

被引:33
作者
Liaury, Kristian [1 ,4 ]
Miyaoka, Tsuyoshi [1 ]
Tsumori, Toshiko [2 ,3 ]
Furuya, Motohide [1 ]
Hashioka, Sadayuki [1 ]
Wake, Rei [1 ]
Tsuchie, Keiko [1 ]
Fukushima, Michiyo [1 ]
Limoa, Erlyn [1 ,4 ]
Tanra, Andi Jayalangkara [4 ]
Horiguchi, Jun [1 ]
机构
[1] Shimane Univ, Fac Med, Dept Psychiat, Izumo, Shimane 6938501, Japan
[2] Shimane Univ, Fac Med, Dept Anat Morphol Neurosci, Izumo, Shimane 6938501, Japan
[3] Prefectural Univ Hiroshima, Fac Hlth & Welf, Dept Nursing, Mihara 7230053, Japan
[4] Hasanuddin Univ, Dept Psychiat, Fac Med, Makassar 90245, South Sulawesi, Indonesia
关键词
Activated microglia; Behavioral test; Gunn rat; Minocycline; Schizophrenia; Unconjugated bilirubin; DOUBLE-BLIND; UNCONJUGATED BILIRUBIN; MICE; INFLAMMATION; INHIBITION; SYMPTOMS; DEFICITS; ANTIPSYCHOTICS; NEUROTOXICITY; TETRACYCLINE;
D O I
10.1016/j.pnpbp.2013.12.017
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Accumulating evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. We previously reported evidence of schizophrenia-like behaviors and microglial activation in Gunn rats. We concluded that the Gunn rat, which exhibits a high concentration of unconjugated bilirubin, may be useful as an animal model of schizophrenia. On the other hand, there have been numerous reports that minocycline is effective in treating schizophrenia. Methods: In the present study, we investigated the effects of minocycline on performance of behavioral tests (prepulse inhibition (PPI) and novel object recognition test (NORT)) after animals received either 40 mg/kg/d of minocycline or vehicle by intraperitoneal (i.p.) injection for 14 consecutive days. Furthermore, we examined the effects of minocycline on microglial activation in the hippocampal dentate gyrus of Gunn rats and Wistar rats. Results: We found that administration of minocycline for 14 days significantly increased the exploratory preference in retention sessions and tended to improve the PPI deficits in Gunn rats. Immunohistochemistry analysis revealed that microglial cells in the minocycline-treated Gunn rat group showed less expression of CD11b compared to vehicle-treated Gunn and Wistar groups. Conclusions: Our findings suggest that minocycline improves recognition memory and attenuates microglial activation in the hippocampal dentate gyrus of Gunn rats. Therefore, minocycline may be a potential therapeutic drug for schizophrenia. (C) 2013 Published by Elsevier Inc.
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收藏
页码:184 / 190
页数:7
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