Department of Biochemistry and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Neuroscience, Faculty of Advanced Technologist in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Neurosci Lett. 2022 Jan 23;770:136354. doi: 10.1016/j.neulet.2021.136354. Epub 2021 Nov 18.
Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) is one of the most important genes associated with schizophrenia. In this study, 45 male Wistar rats were divided into 5 groups of saline, control, ketamine, clozapine, and risperidone. Animals in ketamine, risperidone, and clozapine groups received ketamine (30 mg/kg-i.p.) for 10 days. After the last injection of ketamine, we started injecting clozapine (7.5 mg/kg-i.p.), risperidone (1 mg/kg-i.p.), up to 28 days. Twenty-four hours after the last injection, open field, social interaction, and elevated plus-maze tests and gene expression in hippocampus were performed. The results of the social interaction test revealed a significant decrease in cumulative time with ketamine, compared with the saline group, and an increase with clozapine and risperidone compared with the ketamine group. Moreover, results from the elevated plus-maze test demonstrated a critical decrease in open arm time and increase in close arm time with ketamine compared with saline, as well as increased in open arm time with risperidone compared with ketamine. Further results revealed a significant increase in rearing and grooming with ketamine compared to saline, as well as a decrease with risperidone and clozapine compared to ketamine. There were no significant differences in CACNA1C gene expression between groups in the rat hippocampus. In brief, the results of this study indicated that clozapine and risperidone could partially improve cognitive impairments in the rat. However, our findings demonstrated that this treatment is not related to CACNA1C gene expression.
钙电压门控通道亚基 α1 C（CACNA1C）是与精神分裂症关联最密切的重要基因之一。在这项研究中，将 45 只雄性 Wistar 大鼠分为盐水、对照组、氯胺酮、氯氮平和利培酮 5 组。氯胺酮、利培酮和氯氮平组的动物接受氯胺酮（30mg/kg-i.p.）治疗 10 天。在最后一次氯胺酮注射后，我们开始注射氯氮平（7.5mg/kg-i.p.）和利培酮（1mg/kg-i.p.），持续 28 天。最后一次注射后 24 小时，进行旷场、社会互动和高架十字迷宫测试以及海马基因表达。社会互动测试的结果显示，与盐水组相比，氯胺酮组的累积时间明显减少，而氯氮平和利培酮组则增加。此外，高架十字迷宫测试的结果表明，与盐水组相比，氯胺酮组的开放臂时间显著减少，而封闭臂时间增加，而与氯胺酮组相比，利培酮组的开放臂时间增加。进一步的结果表明，与盐水组相比，氯胺酮组的理毛和理毛次数显著增加，而氯氮平和利培酮组则减少。在大鼠海马体中，各组间 CACNA1C 基因表达无显著差异。总之，本研究结果表明，氯氮平和利培酮可部分改善大鼠的认知障碍。然而，我们的研究结果表明，这种治疗与 CACNA1C 基因表达无关。
