Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons

IF 6.7 2区医学 Q1 NEUROSCIENCES

Progress in Neurobiology Pub Date : 2024-11-01 DOI:10.1016/j.pneurobio.2024.102682

E. Ramírez-Sánchez, A. Mondragón-García, J. Garduño, F. Hernández-Vázquez, S. Ortega-Tinoco, S. Hernández-López

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Abstract

The hypothalamic arcuate nucleus (ARC) contains two main populations of neurons essential for energy homeostasis: neuropeptide Y (NPY) neurons, which are orexigenic and stimulate food intake, and proopiomelanocortin (POMC) neurons, which have an anorexigenic effect. Located near the blood-brain barrier, ARC neurons sense blood-borne signals such as leptin, insulin, and glucose. Exogenous substances, such as nicotine, can also alter ARC neuron activity and energy balance. Nicotine, an addictive drug used worldwide, inhibits appetite, and reduces body weight, although its mechanisms in regulating ARC neurons are not well understood. Using electrophysiological techniques in brain slices, we investigated the effects of nicotine on POMC and NPY neurons at physiological glucose concentrations. We found that nicotine increased the firing rate of POMC and inhibited NPY neurons. Additionally, nicotine-enhanced glutamatergic inputs to POMC cells and GABAergic inputs to NPY neurons, mediated by α7 and α4β2 nicotinic acetylcholine receptors (nAChRs), respectively. These findings can contribute to the understanding of the anorexigenic effects of nicotine in smokers.

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尼古丁对下丘脑弓状核 POMC 和 NPY 神经元的相反作用

下丘脑弓状核（ARC）包含对能量平衡至关重要的两大类神经元：神经肽 Y（NPY）神经元和原绒毛膜促皮质素（POMC）神经元，前者具有促食欲作用，后者具有厌食作用。ARC 神经元位于血脑屏障附近，能感知瘦素、胰岛素和葡萄糖等血源性信号。尼古丁等外源性物质也会改变 ARC 神经元的活动和能量平衡。尼古丁是一种全球通用的成瘾性药物，可抑制食欲并减轻体重，但其调节 ARC 神经元的机制尚不十分清楚。我们利用脑片电生理技术，研究了尼古丁在生理葡萄糖浓度下对 POMC 和 NPY 神经元的影响。我们发现，尼古丁能提高 POMC 的发射率并抑制 NPY 神经元。此外，尼古丁还分别通过α7和α4β2烟碱乙酰胆碱受体（nAChRs）介导，增强了POMC细胞的谷氨酸能输入和NPY神经元的GABA能输入。这些发现有助于了解尼古丁对吸烟者的厌食效应。

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来源期刊

Progress in Neurobiology 医学-神经科学

CiteScore

12.80

自引率

1.50%

发文量

107

审稿时长

33 days

期刊介绍： Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.