Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons.
Proc Natl Acad Sci U S A
; 111(33): 12228-33, 2014 Aug 19.
Article
de En
| MEDLINE
| ID: mdl-25071212
ABSTRACT
L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transduction du signal
/
Expression des gènes
/
N-Méthyl-aspartate
/
Acide lactique
/
Plasticité neuronale
/
Neurones
Limites:
Animals
Langue:
En
Journal:
Proc Natl Acad Sci U S A
Année:
2014
Type de document:
Article