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Microglial activation induced by LPS mediates excitation of the hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla
Tae Hee Han1 (Graduate Student), Heow Won Lee1 (Graduate Student), Eun A Kang1 (Graduate Student), Min Seok Song1 (Graduate Student), So Yeong Lee 1,* (Professor), Pan Dong Ryu1 (Professor)
1Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University
Abstract
Microglia is known to be activated in the hypothalamic paraventricular nucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in neuronal plasticity of presympathetic PVN neurons associated with the modulation of sympathetic outflow remains poorly investigated. In this study, we investigated the direct link of microglial activation with the spontaneous firing rate and the underlying synaptic mechanisms in PVN neurons projecting to the RVLM. Systemic LPS injection induced microglia activation in the PVN, increased the frequency of the spontaneous firing activity of PVN-RVLM neurons, reduced GABAergic inputs into PVN-RVLM neurons, and increased plasma NE levels and heart rate. Systemic minocycline injection blocked all the observed LPS-induced effects. Our results indicate that LPS induces an elevated firing rate and a decrease in GABAergic transmission in PVN-RVLM neurons associated with sympathetic outflow and that the alteration is largely due to the activation of microglia. Our findings provide some insights in terms of the role of microglia activation in regulating neuronal activity in PVN-RVLM neurons associated with modulation of sympathetic outflow commonly seen in cardiovascular diseases.
Abstract, Accepted Manuscript(in press) [Submitted on August 2, 2021, Accepted on October 22, 2021]
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