通过使条状胆固醇活性正常化,thalamostriatal退化的认知效应得到改善
Serena Becchi1, Billy Chieng1, Laura A Bradfield2
1School of Psychology, Faculty of Science, University of New South Wales, Sydney, Australia.
Science advances
|June 23, 2023
概括
神经炎症通过影响对状体质 (Pf) 输入到背中状体 (DMS) 来损害目标导向的行动. 赛列吉林治疗通过恢复胆固醇内部神经元功能来挽救这些认知缺陷.
科学领域:
- 神经科学是一个神经科学.
- 神经炎症研究 神经炎症研究
- 认知功能研究 认知功能研究
背景情况:
- 抛物线丘脑 (Pf) 神经元的损失及其背中条体 (DMS) 投射与勒维体疾病 (LBD) 和帕金森病痴呆症 (PDD) 有关.
- 神经炎症是这些神经元损失和相关认知障碍的可疑驱动因素.
- 状胆性内部神经元 (CINs) 在灵活的目标导向行为中起着至关重要的作用.
研究的目的:
- 调查Pf-DMS输入在调节CIN活动和行动结果 (AO) 关联编码中的作用.
- 为了确定神经炎症对这些过程的影响.
- 评估塞列吉林在缓解神经炎症引起的认知缺陷方面的治疗潜力.
主要方法:
- 利用大鼠模型研究Pf-DMS通路功能的影响在AO应急工作中的轮班期间对CIN发射模式.
- 在Pf中诱导的神经炎症,以评估其对目标导向控制和CIN活动的影响.
- 通过外周和DMS内部给药selegiline,以评估其救生效应.
主要成果:
- 在AO应急班次期间,Pf-DMS输入对于CIN的爆发暂停发射模式至关重要,这对于灵活的目标导向行动至关重要.
- 在Pf中的神经炎症扰乱了CIN活动变化,并在应急班次后损害了目标导向控制.
- 通过外周和DMS内部给药,塞列吉林成功地恢复了CIN功能和目标控制.
结论:
- 对于适应性认知灵活性来说,Pf-DMS途径至关重要,特别是在响应不断变化的行动-结果关联时.
- 神经炎症破坏了这种途径,导致在LBD和PDD中观察到的认知缺陷.
- 塞利吉林通过增强CIN功能来证明治疗与神经炎症相关的认知障碍的治疗潜力.
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