Kristian Liaury1, Tsuyoshi Miyaoka2, Toshiko Tsumori3, Motohide Furuya4, Sadayuki Hashioka5, Rei Wake6, Keiko Tsuchie7, Michiyo Fukushima8, Erlyn Limoa9, Andi Jayalangkara Tanra10, Jun Horiguchi11. 1. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, South Sulawesi, Indonesia. Electronic address: krizbox@hotmail.com. 2. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: miyanyan@med.shimane-u.ac.jp. 3. Department of Anatomy Morphological Neuroscience, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; Department of Nursing, Faculty of Health and Welfare, Prefectural University of Hiroshima, 1-1 Gakuen-cho, Mihara 723-0053, Japan. Electronic address: t-tsumori@pu-hiroshima.ac.jp. 4. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: pancho@med.shimane-u.ac.jp. 5. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: hashioka@med.shimane-u.ac.jp. 6. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: rei@med.shimane-u.ac.jp. 7. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: keits@med.shimane-u.ac.jp. 8. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: mtaki@med.shimane-u.ac.jp. 9. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, South Sulawesi, Indonesia. Electronic address: erlynliem@yahoo.com. 10. Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, South Sulawesi, Indonesia. Electronic address: ajtanra@yahoo.com. 11. Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: jhorigu@med.shimane-u.ac.jp.
Abstract
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 40mg/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 14days 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.
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 40mg/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 14days 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.
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