准葡萄糖抑制的海马CCK内部神经元可以防止饮食诱导的肥胖症的认知障碍
Taylor Landry1, Laura Perrault2, David Melville3
1Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
短期高脂肪饮食 (HFD) 通过过度激活特定的大脑细胞来损害记忆力. 向这些细胞或酶酸激酶M2 (PKM2) 可能可以防止与代谢障碍相关的认知衰退.
科学领域:
- 神经科学是一个神经科学.
- 代谢障碍 代谢障碍 代谢障碍
- 细胞生物学 细胞生物学
背景情况:
- 代谢障碍会增加认知能力下降的风险.
- 高脂肪饮食 (HFD) 有关,但机制尚不清楚.
- 饮食对大脑葡萄糖代谢和神经元功能的影响需要阐明.
研究的目的:
- 研究短期HFD (stHFD) 如何影响记忆处理.
- 确定细胞和分子机制,将HFD与认知障碍联系起来.
- 探索饮食引起的认知衰退的治疗目标.
主要方法:
- 利用一个小鼠模型的stHFD消费.
- 测量了牙状 (DG) 神经元活动,特别是胆囊托基宁表达内神经元 (CCK-INs).
- 评估葡萄糖的可用性,PKM2酸化,并实施干预措施以恢复正常功能.
主要成果:
- stHFD诱导了DG CCK-INs的过度活动,与降低的DG葡萄糖和增加的PKM2酸化有关.
- 恢复葡萄糖,减少PKM2表达或抑制PKM2活动,使CCK-IN活动正常化并挽救记忆缺陷.
- 在饮食诱导的肥胖模型中,预防CCK-IN过活性或PKM2酸化可以防止长期认知障碍.
结论:
- 由于代谢压力,stHFD通过DG CCK-INs的过度活动来破坏记忆.
- 降低DG葡萄糖和增加PKM2酸化是关键的分子事件.
- 总局CCK-INs和PKM2代表了与代谢障碍相关的认知衰退的潜在治疗点.
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