Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.

Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary ne...

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Autores principales:	Luigi Bozzo, Julien Puyal, Jean-Yves Chatton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b1189d6593ce44df9772996f8c428b16
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spelling	oai:doaj.org-article:b1189d6593ce44df9772996f8c428b162021-11-18T09:00:06ZLactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.1932-620310.1371/journal.pone.0071721https://doaj.org/article/b1189d6593ce44df9772996f8c428b162013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23951229/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.Luigi BozzoJulien PuyalJean-Yves ChattonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71721 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luigi Bozzo Julien Puyal Jean-Yves Chatton Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
description	Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.
format	article
author	Luigi Bozzo Julien Puyal Jean-Yves Chatton
author_facet	Luigi Bozzo Julien Puyal Jean-Yves Chatton
author_sort	Luigi Bozzo
title	Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
title_short	Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
title_full	Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
title_fullStr	Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
title_full_unstemmed	Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
title_sort	lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b1189d6593ce44df9772996f8c428b16
work_keys_str_mv	AT luigibozzo lactatemodulatestheactivityofprimarycorticalneuronsthroughareceptormediatedpathway AT julienpuyal lactatemodulatestheactivityofprimarycorticalneuronsthroughareceptormediatedpathway AT jeanyveschatton lactatemodulatestheactivityofprimarycorticalneuronsthroughareceptormediatedpathway
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Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.

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