Astrocytic Metabolic Control of Orexinergic Activity in the Lateral Hypothalamus Regulates Sleep and Wake Architecture

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jul 16

PMID 39013907

Authors

Alice Braga

Martina Chiacchiaretta

Luc Pellerin

Dong Kong

Philip G Haydon

Affiliations

Soon will be listed here.

Abstract

Neuronal activity undergoes significant changes during vigilance states, accompanied by an accommodation of energy demands. While the astrocyte-neuron lactate shuttle has shown that lactate is the primary energy substrate for sustaining neuronal activity in multiple brain regions, its role in regulating sleep/wake architecture is not fully understood. Here we investigated the involvement of astrocytic lactate supply in maintaining consolidated wakefulness by downregulating, in a cell-specific manner, the expression of monocarboxylate transporters (MCTs) in the lateral hypothalamus of transgenic mice. Our results demonstrate that reduced expression of MCT4 in astrocytes disrupts lactate supply to wake-promoting orexin neurons, impairing wakefulness stability. Additionally, we show that MCT2-mediated lactate uptake is necessary for maintaining tonic firing of orexin neurons and stabilizing wakefulness. Our findings provide both in vivo and in vitro evidence supporting the role of astrocyte-to-orexinergic neuron lactate shuttle in regulating proper sleep/wake stability.

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