21 October 2020
Role of lactate in memory formation
Published online 31 August 2014
The brain’s ability to reorganize its neural pathways based on new experiences is known as neuronal plasticity. This process, which is key to learning and long-term memory, requires astrocytes to transport lactate to neurons1.
However, researchers are not sure how lactate contributes to neuronal plasticity. An international research team has now discovered that transfer of l-lactate from astrocytes to neurons activates specific genes that trigger neuronal plasticity in the neocortex of mice.
The researchers from King Abdullah University of Science and Technology (KAUST), Saudi Arabia, and Ecole Polytechnique Fédérale de Lausanne and Centre Hospitalier Universitaire Vaudois, Switzerland, treated cultured primary neurons from mice neocortex with various doses of l-lactate.
They found that l-lactate treatment increased the expression of plasticity-related genes such as Arc, c-Fos, Zif268 and BDNF in mouse neurons by modulating the activity of N-methyl-d-aspartate receptor, a cell-surface protein at the contact point of two neurons. The findings of this study have been published in PNAS2.
When the researchers treated the cultured neurons with l-pyruvate and d-glucose, the neurons did not express the plasticity genes, indicating that l-lactate selectively activated these genes. Preventing the transport of l-lactate from astrocytes to neurons completely prevented the expression of the genes.
“l-lactate treatment could potentially alleviate symptoms in cognitively impaired patients,” says Pierre Magistretti, a senior author of the study.
- Suzuki, A. et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144, 810-823 (2014)
- Yang, J. et al. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc. Natl Acad. Sci. USA. (2014) http://dx.doi.org/10.1073/pnas.1322912111