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

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Microglia are known to be activated in the hypothalamic paraventricularnucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in the plasticityof presympathetic PVN neurons associated with the modulationof sympathetic outflow remains poorly investigated. Inthis study, we analyzed the direct link between microglial activationand spontaneous firing rate along with the underlyingsynaptic mechanisms in PVN neurons projecting to the rostralventrolateral medulla (RVLM). Systemic injection of LPS inducedmicroglial activation in the PVN, increased the frequency ofspontaneous firing activity of PVN-RVLM neurons, reducedGABAergic inputs into these neurons, and increased plasma NElevels and heart rate. Systemic minocycline injection blockedall the observed LPS-induced effects. Our results indicate thatLPS increases the firing rate and decreases GABAergic transmissionin PVN-RVLM neurons associated with sympatheticoutflow and the alteration is largely attributed to the activationof microglia. Our findings provide some insights into the roleof microglial activation in regulating the activity of PVN-RVLMneurons associated with modulation of sympathetic outflow incardiovascular diseases.

Abstract

Microglia are known to be activated in the hypothalamic paraventricularnucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in the plasticityof presympathetic PVN neurons associated with the modulationof sympathetic outflow remains poorly investigated. Inthis study, we analyzed the direct link between microglial activationand spontaneous firing rate along with the underlyingsynaptic mechanisms in PVN neurons projecting to the rostralventrolateral medulla (RVLM). Systemic injection of LPS inducedmicroglial activation in the PVN, increased the frequency ofspontaneous firing activity of PVN-RVLM neurons, reducedGABAergic inputs into these neurons, and increased plasma NElevels and heart rate. Systemic minocycline injection blockedall the observed LPS-induced effects. Our results indicate thatLPS increases the firing rate and decreases GABAergic transmissionin PVN-RVLM neurons associated with sympatheticoutflow and the alteration is largely attributed to the activationof microglia. Our findings provide some insights into the roleof microglial activation in regulating the activity of PVN-RVLMneurons associated with modulation of sympathetic outflow incardiovascular diseases.

참고문헌 (36)

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