Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

Autor: Fiona E. Holmes, Alastair J. MacDonald, Anthony E. Pickering, Kate L. J. Ellacott, Craig Beall
Rok vydání: 2020
Předmět:
Zdroj: Glia
ISSN: 1098-1136
0894-1491
DOI: 10.1002/glia.23774
Popis: A role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated in regulating energy homeostasis. The nucleus of the solitary tract (NTS), within the brainstem dorsal vagal complex (DVC), integrates vagal afferent information from the viscera and plays a role in regulating food intake. We hypothesized that astrocytes in this nucleus respond to, and influence, food intake. Mice fed high‐fat chow for 12 hr during the dark phase showed NTS astrocyte activation, reflected in an increase in the number (65%) and morphological complexity of glial‐fibrillary acidic protein (GFAP)‐immunoreactive cells adjacent to the area postrema (AP), compared to control chow fed mice. To measure the impact of astrocyte activation on food intake, we delivered designer receptors exclusively activated by designer drugs (DREADDs) to DVC astrocytes (encompassing NTS, AP, and dorsal motor nucleus of the vagus) using an adeno‐associated viral (AAV) vector (AAV‐GFAP‐hM3Dq_mCherry). Chemogenetic activation with clozapine‐N‐oxide (0.3 mg/kg) produced in greater morphological complexity in astrocytes and reduced dark‐phase feeding by 84% at 4 hr postinjection compared with vehicle treatment. hM3Dq‐activation of DVC astrocytes also reduced refeeding after an overnight fast (71% lower, 4 hr postinjection) when compared to AAV‐GFAP‐mCherry expressing control mice. DREADD‐mediated astrocyte activation did not impact locomotion. hM3Dq activation of DVC astrocytes induced c‐FOS in neighboring neuronal feeding circuits (including in the parabrachial nucleus). This indicates that NTS astrocytes respond to acute nutritional excess, are involved in the integration of peripheral satiety signals, and can reduce food intake when activated.
MAIN POINTS High‐fat feeding in mice induces morphological changes in brainstem astrocytes.Chemogenetic activation of astrocytes in the dorsal vagal complex reduces feeding.Glial activation recruits local neural circuits known to be involved in food intake. Chemogenetic activation of astrocytes in the mouse dorsal vagal complex reduces food intake and activates local neuronal circuits
Databáze: OpenAIRE
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