前额叶皮层特异性的Dcc删除会诱导与精神分裂症相关的行为表型,并且无法通过奥兰zapine治疗来挽救
Jing Sun1, Qijie Cong1, Tingkai Sun1
1Neurobiology & Mitochondrial Key Laboratory, Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
European journal of pharmacology
|August 4, 2023
概括
在结直肠癌 (Dcc) 中被删除的基因变异与精神疾病有关. 在小鼠中,Dcc基因的淘汰会损害与精神分裂症相关的行为,并影响抗精神病药物的疗效,这表明它在治疗耐药性方面发挥了作用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 基因组研究将被删除的结直肠癌 (Dcc) 基因变异与精神疾病联系起来.
- 在精神分裂症 (SCZ) 相关行为和抗精神病药物疗效中,Dcc的确切功能仍然不清楚.
研究的目的:
- 用小鼠模型研究Dcc在SCZ相关行为异常中的作用.
- 在体内探索Dcc敲击对抗精神病药物的疗效的影响.
主要方法:
- 在成年C57BL/6小鼠中生成了前额叶皮层特异性的Dcc淘汰 (KD) 鼠标模型.
- 在Dcc KD小鼠中评估注意力缺陷和运动运动活动.
- 评估了 olanzapine 对 Dcc KD 和 MK801 治疗小鼠 SCZ 相关行为的影响.
主要成果:
- 在小鼠模型中,Dcc删除对SCZ相关行为作出了重要贡献.
- 在接受MK801治疗的小鼠中,olanzapine有效地挽救了SCZ相关的行为,但在Dcc KD小鼠中没有.
- 前额叶皮层的Dcc敲击导致了谷氨基酶功能障碍,影响了谷氨基胺合成酶和后突触成熟.
结论:
- Dcc在奥兰扎抗精神病作用的机制中起着至关重要的作用.
- 在SCZ中,Dcc删除诱导的谷氨基质功能障碍可能是治疗奥兰扎宾耐药性的基础.
- Dcc KD小鼠模型为研究SCZ机制和抗精神病治疗耐药性提供了一个有价值的平台.
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