| First Author | Braga A | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 5979 |
| PubMed ID | 39013907 | Mgi Jnum | J:351407 |
| Mgi Id | MGI:7702830 | Doi | 10.1038/s41467-024-50166-7 |
| Citation | Braga A, et al. (2024) Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture. Nat Commun 15(1):5979 |
| abstractText | 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. |
