Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture.

Autor: Braga A; Department of Neuroscience, Tufts University School of Medicine, Boston, MA, 02111, USA., Chiacchiaretta M; Department of Neuroscience, Tufts University School of Medicine, Boston, MA, 02111, USA. martina.chiacchiaretta16@gmail.com., Pellerin L; Inserm U1313, University and CHU of Poitiers, 86021, Poitiers, France., Kong D; Department of Neuroscience, Tufts University School of Medicine, Boston, MA, 02111, USA.; Division of Endocrinology, Department of Pediatrics, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Haydon PG; Department of Neuroscience, Tufts University School of Medicine, Boston, MA, 02111, USA. philip.haydon@tufts.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 16; Vol. 15 (1), pp. 5979. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1038/s41467-024-50166-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: