Titre
Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Briquet, M.
Auteure/Auteur
Rocher, A.B.
Auteure/Auteur
Alessandri, M.
Auteure/Auteur
Rosenberg, N.
Auteure/Auteur
de Castro Abrantes, H.
Auteure/Auteur
Wellbourne-Wood, J.
Auteure/Auteur
Schmuziger, C.
Auteure/Auteur
Ginet, V.
Auteure/Auteur
Puyal, J.
Auteure/Auteur
Pralong, E.
Auteure/Auteur
Daniel, R.T.
Auteure/Auteur
Offermanns, S.
Auteure/Auteur
Chatton, J.Y.
Auteure/Auteur
Liens vers les unités
ISSN
1559-7016
Statut éditorial
Publié
Date de publication
2022-09
Volume
42
Numéro
9
Première page
1650
Dernière page/numéro d’article
1665
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Lactate can be used by neurons as an energy substrate to support their activity. Evidence suggests that lactate also acts on a metabotropic receptor called HCAR1, first described in the adipose tissue. Whether HCAR1 also modulates neuronal circuits remains unclear. In this study, using qRT-PCR, we show that HCAR1 is present in the human brain of epileptic patients who underwent resective surgery. In brain slices from these patients, pharmacological HCAR1 activation using a non-metabolized agonist decreased the frequency of both spontaneous neuronal Ca <sup>2+</sup> spiking and excitatory post-synaptic currents (sEPSCs). In mouse brains, we found HCAR1 expression in different regions using a fluorescent reporter mouse line and in situ hybridization. In the dentate gyrus, HCAR1 is mainly present in mossy cells, key players in the hippocampal excitatory circuitry and known to be involved in temporal lobe epilepsy. By using whole-cell patch clamp recordings in mouse and rat slices, we found that HCAR1 activation causes a decrease in excitability, sEPSCs, and miniature EPSCs frequency of granule cells, the main output of mossy cells. Overall, we propose that lactate can be considered a neuromodulator decreasing synaptic activity in human and rodent brains, which makes HCAR1 an attractive target for the treatment of epilepsy.
PID Serval
serval:BIB_710024816385
PMID
DOI données de recherche
10.5281/zenodo.6372562
Open Access
Oui
Date de création
2022-03-14T08:07:15.602Z
Date de création dans IRIS
2025-05-20T22:25:26Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
Briquet et al- JCBFM 2022.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.38 MB
Format
Adobe PDF
PID Serval
serval:BIB_710024816385.P001
URN
urn:nbn:ch:serval-BIB_7100248163855
Somme de contrôle
(MD5):e4803a225a0a484fed6c25629200f744