Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells.
Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells.
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α7烟碱型乙酰胆碱受体的激活可预防小胶质细胞诱导的下丘脑神经元细胞炎症及胰岛素抵抗。
DOI：
10.3390/cells11142195
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发表时间：
2022-07-14
期刊：
影响因子：
6
通讯作者：
Torsoni, Marcio Alberto
中科院分区：
文献类型：
--
作者：
do Amaral, Camila Libardi;Alves Martins, Isis de Cassia;Costa Veras, Alana Carolina;Simabuco, Fernando Moreira;Ross, Michael Glenn;Desai, Mina;Ignacio-Souza, Leticia Martins;Milanski, Marciane;Torsoni, Adriana Souza;Torsoni, Marcio Alberto
神经元下丘脑胰岛素抵抗与能量平衡失调有关，并导致多种神经退行性疾病的发病。它的发展与主要由活化的小胶质细胞协调的神经炎症过程密切相关。在这方面，我们的研究旨在研究一个在下丘脑中高度表达并参与炎症过程调节的靶点，但在神经元胰岛素抵抗的背景下仍然研究不足：α7烟碱乙酰胆碱受体（α 7 nAchR）。在此，我们发现，暴露于促炎性小胶质细胞条件培养基（MCM）的mHypoA-2/29神经元显示出促炎性细胞因子IL-6、IL-1β和TNF-α的更高表达，此外还出现胰岛素抵抗。用选择性激动剂PNU-282987激活α 7 nAchR可通过抑制NF-κB核转位和增加IL-10和tristetraprolin（TTP）基因表达来预防小胶质细胞诱导的炎症。α 7 nAchR的抗炎作用还伴随着胰岛素敏感性的改善和神经变性相关标志物（例如GSK 3和tau）的较低激活。总之，我们发现，下丘脑神经元中α 7 nAchR抗炎信号的激活发挥神经保护作用，并防止由小胶质细胞分泌的促炎介质诱导的胰岛素抵抗的发展。
Neuronal hypothalamic insulin resistance is implicated in energy balance dysregulation and contributes to the pathogenesis of several neurodegenerative diseases. Its development has been intimately associated with a neuroinflammatory process mainly orchestrated by activated microglial cells. In this regard, our study aimed to investigate a target that is highly expressed in the hypothalamus and involved in the regulation of the inflammatory process, but still poorly investigated within the context of neuronal insulin resistance: the α7 nicotinic acetylcholine receptor (α7nAchR). Herein, we show that mHypoA-2/29 neurons exposed to pro-inflammatory microglial conditioned medium (MCM) showed higher expression of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, in addition to developing insulin resistance. Activation of α7nAchR with the selective agonist PNU-282987 prevented microglial-induced inflammation by inhibiting NF-κB nuclear translocation and increasing IL-10 and tristetraprolin (TTP) gene expression. The anti-inflammatory role of α7nAchR was also accompanied by an improvement in insulin sensitivity and lower activation of neurodegeneration-related markers, such as GSK3 and tau. In conclusion, we show that activation of α7nAchR anti-inflammatory signaling in hypothalamic neurons exerts neuroprotective effects and prevents the development of insulin resistance induced by pro-inflammatory mediators secreted by microglial cells.
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影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
阿尔茨海默氏病的GSK3假设。
影响因子：
4.7
作者：
Hooper C;Killick R;Lovestone S
通讯作者：
Lovestone S
DOI：
10.1016/j.bbagrm.2013.02.003
发表时间：
2013-06
影响因子：
4.7
作者：
Brooks, Seth A.;Blackshear, Perry J.
通讯作者：
Blackshear, Perry J.
影响因子：
4.7
作者：
Moser, N.;Mechawar, N.;Wevers, A.
通讯作者：
Wevers, A.
影响因子：
3.1
作者：
Gonzalez-Reyes, Rodrigo E.;Aliev, Gjumrakch;Barreto, George E.
通讯作者：
Barreto, George E.