Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 09 2023
16 09 2023
Historique:
received:
13
12
2022
accepted:
07
09
2023
medline:
18
9
2023
pubmed:
17
9
2023
entrez:
16
9
2023
Statut:
epublish
Résumé
Microglia, the innate immune cells of the central nervous system, actively participate in brain development by supporting neuronal maturation and refining synaptic connections. These cells are emerging as highly metabolically flexible, able to oxidize different energetic substrates to meet their energy demand. Lactate is particularly abundant in the brain, but whether microglia use it as a metabolic fuel has been poorly explored. Here we show that microglia can import lactate, and this is coupled with increased lysosomal acidification. In vitro, loss of the monocarboxylate transporter MCT4 in microglia prevents lactate-induced lysosomal modulation and leads to defective cargo degradation. Microglial depletion of MCT4 in vivo leads to impaired synaptic pruning, associated with increased excitation in hippocampal neurons, enhanced AMPA/GABA ratio, vulnerability to seizures and anxiety-like phenotype. Overall, these findings show that selective disruption of the MCT4 transporter in microglia is sufficient to alter synapse refinement and to induce defects in mouse brain development and adult behavior.
Identifiants
pubmed: 37717033
doi: 10.1038/s41467-023-41502-4
pii: 10.1038/s41467-023-41502-4
pmc: PMC10505217
doi:
Substances chimiques
Lactic Acid
33X04XA5AT
Membrane Transport Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5749Informations de copyright
© 2023. Springer Nature Limited.
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