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转化生长因子β-2在WT和BMAL1缺陷的下丘脑神经元中均有节奏表达,并调节神经Y:Palmitate扰乱

Aws F Mustafa¹, Wenyuan He¹, Denise D Belsham²

¹Department of Physiology, University of Toronto, Ontario, Canada.

Molecular and cellular endocrinology

|November 10, 2024

概括

在下丘脑中转化生长因子β2 (TGF-β2) 与昼夜节律,食控制和神经炎症有关. 肥胖会破坏TGF-β2信号传递,影响神经Y (NPY) 表达和能量恒温.

科学领域:

神经科学是一个神经科学.
内分泌学在内分泌学.
分子生物学分子生物学

背景情况:

下丘脑通过神经Y (NPY) 神经元调节能量稳态.
在肥胖的发展过程中,下丘脑中的神经炎症先于外周变化.
转化生长因子β (TGF-β) 细胞因子与下丘脑神经炎症有关,但尚未完全理解.

研究的目的:

研究TGF-β信号元件在下丘脑功能中的作用,特别是它们与昼夜节律和NPY表达的联系.
探索肥胖相关的因素,如棕酸盐如何影响TGF-β信号传递和下丘脑的NPY调节.

主要方法:

在下丘脑组织和细胞培养中分析Tgfb 1-3和受体 (Tgfbr1,Tgfbr2) 表达.
在正常和BMAL1缺陷的下丘脑神经元中评估Tgfb2mRNA昼夜节律性.
用TGF-β2对NPY表达神经元进行治疗,以研究对昼夜振荡器和Npy mRNA的影响.
研究棕酸对TGF-β信号传递,BMAL1结合和Npy mRNA的影响,以及TGFBRI对抗性的影响.

主要成果:

Tgfb 1-3及其受体在下丘脑表达高.
Tgfb2mRNA在下丘脑神经元中表现出昼夜表达,独立于BMAL1.1.
在TGF-β2治疗上调核心昼夜基因 (Bmal1,Nr1d1) 和Npy mRNA.
棕酸破坏了TGF-β信号传递,增加了BMAL1与Tgfb2的结合,并调节了Npy mRNA;TGFBRI对抗作用减轻了这一点.

结论:

脑下神经元TGF-β2集成了昼夜节律,为神经控制和神经炎症提供营养.
营养过多会破坏TGF-β2信号传递,导致下丘脑功能障碍和潜在的肥胖.
了解这些机制对于制定对抗肥胖和相关代谢障碍的策略至关重要.

关键词:

循环节律循环节律是指循环节律.下丘脑的下丘脑是什么意思神经炎症是一种神经炎症.神经酸Y 神经酸Y 棕酸盐是一种棕酸盐.转化增长因子β的转化增长因子β.

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