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  Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue

Briquet, M., Rocher, A.-B., Alessandri, M., Rosenberg, N., Abrantes, H. d. C., Wellbourne-Wood, J., et al. (2022). Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 0271678X221080324. doi:10.1177/0271678X221080324.

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 Creators:
Briquet, Marc, Author
Rocher, Anne-Berengere, Author
Alessandri, Maxime, Author
Rosenberg, Nadia, Author
Abrantes, Haissa de Castro, Author
Wellbourne-Wood, Joel, Author
Schmuziger, Celine, Author
Ginet, Vanessa, Author
Puyal, Julien, Author
Pralong, Etienne, Author
Daniel, Roy Thomas, Author
Offermanns, Stefan1, Author              
Chatton, Jean-Yves, Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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 Abstract: 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 Ca2+ 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.

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 Dates: 2022-03-03
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: ISI: 000765816200001
DOI: 10.1177/0271678X221080324
PMID: 35240875
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Title: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: 0271678X221080324 Start / End Page: - Identifier: ISSN: 0271-678X