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LPS 诱导的小胶质细胞活化介导投射到延髓头端腹外侧区的下丘脑室旁核神经元的兴奋。

Microglial activation induced by LPS mediates excitation of neurons in the hypothalamic paraventricular nucleus projecting to the rostral ventrolateral medulla.

机构信息

Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.

出版信息

BMB Rep. 2021 Dec;54(12):620-625. doi: 10.5483/BMBRep.2021.54.12.105.

DOI:10.5483/BMBRep.2021.54.12.105
PMID:34814975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8728541/
Abstract

Microglia are known to be activated in the hypothalamic paraventricular nucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in the plasticity of presympathetic PVN neurons associated with the modulation of sympathetic outflow remains poorly investigated. In this study, we analyzed the direct link between microglial activation and spontaneous firing rate along with the underlying synaptic mechanisms in PVN neurons projecting to the rostral ventrolateral medulla (RVLM). Systemic injection of LPS induced microglial activation in the PVN, increased the frequency of spontaneous firing activity of PVN-RVLM neurons, reduced GABAergic inputs into these neurons, and increased plasma NE levels and heart rate. Systemic minocycline injection blocked all the observed LPS-induced effects. Our results indicate that LPS increases the firing rate and decreases GABAergic transmission in PVN-RVLM neurons associated with sympathetic outflow and the alteration is largely attributed to the activation of microglia. Our findings provide some insights into the role of microglial activation in regulating the activity of PVN-RVLM neurons associated with modulation of sympathetic outflow in cardiovascular diseases. [BMB Reports 2021; 54(12): 620-625].

摘要

小胶质细胞在患有心血管疾病的大鼠下丘脑室旁核(PVN)中被激活是已知的。然而,小胶质细胞激活在与交感神经输出调节相关的前交感 PVN 神经元可塑性中的确切作用仍未得到充分研究。在这项研究中,我们分析了小胶质细胞激活与投射到延髓头侧腹外侧区(RVLM)的 PVN 神经元的自发放电率之间的直接联系,以及潜在的突触机制。系统注射 LPS 诱导 PVN 中的小胶质细胞激活,增加了 PVN-RVLM 神经元的自发放电活动频率,减少了这些神经元的 GABA 能传入,并增加了血浆去甲肾上腺素水平和心率。系统中小菌素注射阻断了所有观察到的 LPS 诱导的作用。我们的结果表明,LPS 增加了与交感神经输出相关的 PVN-RVLM 神经元的放电率并降低了 GABA 能传递,这种改变在很大程度上归因于小胶质细胞的激活。我们的发现为小胶质细胞激活在调节心血管疾病中与交感神经输出调节相关的 PVN-RVLM 神经元活性中的作用提供了一些见解。[BMB 报告 2021;54(12):620-625]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/3c468e4435e6/bmb-54-12-620-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/98e50c5fa836/bmb-54-12-620-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/fb5e39045df8/bmb-54-12-620-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/d472baf2b4c5/bmb-54-12-620-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/3c468e4435e6/bmb-54-12-620-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/98e50c5fa836/bmb-54-12-620-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/fb5e39045df8/bmb-54-12-620-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/d472baf2b4c5/bmb-54-12-620-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/8728541/3c468e4435e6/bmb-54-12-620-f4.jpg

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