Striatal astrocytes modulate behavioral flexibility and whole-body metabolism in mice
Nat Commun. 2025-07-07; 16(1):
DOI: 10.1038/s41467-025-60968-y
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https://www.bordeaux-neurocampus.fr/11835
Montalban E(1), Ansoult A(2), Herrera Moro Chao D(2), Pham C(3), Franco C(3),
Contini A(4), Castel J(2), Hassouna R(2), Hardonk MH(2), Petitbon A(4), Foppen
E(2), Gangarossa G(2), Trifilieff P(4), Li D(3), Luquet S(5), Martin C(6).
Author information:
(1)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France. .
(2)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France.
(3)Sorbonne Université, CNRS, Inserm, Institut de Biologie Paris-Seine,
Neuro-SU, Paris, France.
(4)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France.
(5)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France. .
(6)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France. .
Brain circuits in reward-associated behaviors are potent drivers of feeding
behavior but also recently emerged as regulator of metabolism. Short or chronic
exposures to caloric food alter brain structures and are associated with
increased astrocytes reactivity and pro-inflammatory responses in both mice and
humans. However, the role of striatal astrocytes in regulating adaptive and
maladaptive behavioral and metabolic responses to energy-dense food remains
elusive. In this study we reveal that chemogenetic manipulation of the
astrocytes in striatal structures can exert a direct effect on peripheral
metabolism in male mice, and that manipulation of astrocytes in the dorsal
striatum can alter peripheral metabolism and is sufficient to restore cognitive
deficit induced by chronic high fat high sucrose (HFHS) diet exposure in obese
mice. Altogether, this work reveals a yet unappreciated role for striatal
astrocytes as a direct operator of flexible behavior and metabolic control.
© 2025. The Author(s).
DOI: 10.1038/s41467-025-60968-y
PMCID: PMC12234688
PMID: 40624006 [Indexed for MEDLINE]
Conflict of interest statement: Competing interests: The authors declare no
competing interests