- 作者：Kristian Liaury ; Tsuyoshi Miyaoka ; Toshiko Tsumori ; Motohide Furuya ; Sadayuki Hashioka ; Rei Wake ; Keiko Tsuchie ; Michiyo Fukushima ; Erlyn Limoa ; Andi Jayalangkara Tanra ; Jun Horiguchi
- 关键词：UCB ; unconjugated bilirubin ; PPI ; prepulse inhibition ; NORT ; novel object recognition test ; i.p. ; intraperitoneal ; Iba1 ; ionized calcium binding adaptor molecule 1 ; ITGAM ; integrin alpha M ; CD11b ; cluster of differentiation molecule 11B ; DG ; dentate gyrus ; SGZ ; subgranular zone ; GL ; granular layer ; ML ; molecular layer ; PB ; phosphate buffer ; PBS ; phosphate buffer saline ; ABC ; avidin&ndash ; biotin peroxidase complex ; ANOVA ; analysis of variance
- 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
- 出版年：3 April, 2014
- 年：2014
- 卷：50
- 期：Complete
- 页码：184-190
- 全文大小：1344 K
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.