Article ; Online: Exogenous l-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice.
Journal of neuroscience research
2021 Volume 99, Issue 5, Page(s) 1433–1447
Abstract: l-Lactate is an energetic and signaling molecule that may be produced through astrocyte-specific aerobic glycolysis and is elevated in striatal muscle during intensive exercise. l-Lactate has been shown to promote neurotrophic gene expression through ... ...
| Abstract | l-Lactate is an energetic and signaling molecule that may be produced through astrocyte-specific aerobic glycolysis and is elevated in striatal muscle during intensive exercise. l-Lactate has been shown to promote neurotrophic gene expression through astrocytes within the hippocampus, however, its role in neuroplasticity within the striatum remains unknown. This study sought to investigate the role of peripheral sources of l-lactate in promoting astrocyte-specific gene expression and morphology as well as its role in neuroplasticity within the striatum of healthy animals. Using in vitro primary astrocyte cell culture, administration of l-lactate increased the expression of the neurotrophic factors Bdnf, Gdnf, Cntf, and the immediate early gene cFos. l-Lactate's promotion of neurotrophic factor expression was mediated through the lactate receptor HCAR1 since application of the HCAR1 agonist 3,5-DHBA also increased expression of Bdnf in primary astrocytes. Similar to our previous report demonstrating exercise-induced changes in astrocytic structure within the striatum, l-lactate administration to healthy mice led to increased astrocyte morphological complexity as well as astrocyte-specific neurotrophic expression within the striatum. Our study failed to demonstrate an effect of peripheral l-lactate on synaptogenesis or motor behavior. Insufficient levels and/or inadequate delivery of l-lactate through regional cerebral blood flow within the striatum may account for the lack of these benefits. Taken together, these novel findings suggest a potential framework that links peripheral l-lactate production within muscle and intensive exercise with neuroplasticity of specific brain regions through astrocytic function. |
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| MeSH term(s) | Animals ; Astrocytes/drug effects ; Astrocytes/physiology ; Cells, Cultured ; Corpus Striatum/drug effects ; Corpus Striatum/physiology ; Female ; Lactic Acid/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Motor Activity/physiology ; Neurogenesis/drug effects ; Neurogenesis/physiology ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology ; Synapses/drug effects ; Synapses/physiology |
| Chemical Substances | Lactic Acid (33X04XA5AT) |
| Language | English |
| Publishing date | 2021-02-25 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 195324-2 |
| ISSN | 1097-4547 ; 0360-4012 |
| ISSN (online) | 1097-4547 |
| ISSN | 0360-4012 |
| DOI | 10.1002/jnr.24804 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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