Abstract
Adult hippocampal neurogenesis is a dynamic process involved in cognitive functions, like learning and memory. Numerous intrinsic and extrinsic factors regulate and affect hippocampal neurogenesis. An exceptionally beneficial external factor is physical exercise due to the impact of the lactate accumulated during physical effort on neural plasticity. Lactate has recently emerged as one of the most interesting and potent factors in health and disease due to its involvement in the metabolism and signaling of most, if not all, of the cells in the CNS. Herein, we illustrate the effects induced by lactate on the different cell types within the neurogenic niche, in light of their described roles in regulating adult hippocampal neurogenesis.
Similar content being viewed by others
References
Álvarez, Z., Castaño, O., Castells, A. A., Mateos-Timoneda, M. A., Planell, J. A., Engel, E., et al. (2014). Neurogenesis and vascularization of the damaged brain using a lactate-releasing biomimetic scaffold. Biomaterials, 35(17), 4769–4781. https://doi.org/10.1016/j.biomaterials.2014.02.051.
Diaz-Aparicio, I., Paris, I., Sierra-Torre, V., Plaza-Zabala, A., Rodríguez-Iglesias, N., Márquez-Ropero, M., et al. (2020). Microglia Actively Remodel Adult Hippocampal Neurogenesis through the Phagocytosis Secretome. Journal of Neuroscience, 40(7), 1453–1482. https://doi.org/10.1523/JNEUROSCI.0993-19.2019.
El Hayek, L., Khalifeh, M., Zibara, V., Abi Assaad, R., Emmanuel, N., Karnib, N., et al. (2019). Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived neurotrophic factor (BDNF). Journal of Neuroscience, 39(13), 2369–2382. https://doi.org/10.1523/JNEUROSCI.1661-18.2019.
Fabel, K., Fabel, K., Tam, B., Kaufer, D., Baiker, A., Simmons, N., et al. (2003). VEGF is necessary for exercise-induced adult hippocampal neurogenesis. European Journal of Neuroscience, 18(10), 2803–2812. https://doi.org/10.1111/j.1460-9568.2003.03041.x.
Ichihara, Y., Doi, T., Ryu, Y., Nagao, M., Sawada, Y., & Ogata, T. (2017). Oligodendrocyte progenitor cells directly utilize lactate for promoting cell cycling and differentiation. Journal of Cellular Physiology, 232(5), 986–995. https://doi.org/10.1002/jcp.25690.
Kong, L., Wang, Z., Liang, X., Wang, Y., Gao, L., & Ma, C. (2019). Monocarboxylate transporter 1 promotes classical microglial activation and pro-inflammatory effect via 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3. Journal of Neuroinflammation, 16(1), 240. https://doi.org/10.1186/s12974-019-1648-4.
Lee, Y., Morrison, B. M., Li, Y., Lengacher, S., Farah, M. H., Hoffman, P. N., et al. (2012). Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature, 487(7408), 443–448. https://doi.org/10.1038/nature11314.
Lev-Vachnish, Y., Cadury, S., Rotter-Maskowitz, A., Feldman, N., Roichman, A., Illouz, T., et al. (2019). L-lactate promotes adult hippocampal neurogenesis. Frontiers in Neuroscience, 13, 403. https://doi.org/10.3389/fnins.2019.00403.
Matsui, T., Omuro, H., Liu, Y. F., Soya, M., Shima, T., McEwen, B. S., et al. (2017). Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proceedings of the National Academy of Sciences USA, 114(24), 6358–6363. https://doi.org/10.1073/pnas.1702739114.
Morioka, S., Perry, J. S. A., Raymond, M. H., Medina, C. B., Zhu, Y., Zhao, L., et al. (2018). Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release. Nature, 563(7733), 714–718. https://doi.org/10.1038/s41586-018-0735-5.
Morland, C., Andersson, K. A., Haugen, Ø., Hadzic, A., Kleppa, L., Gille, A., et al. (2017). Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nature Communications, 8, 15557. https://doi.org/10.1038/ncomms15557.
Pellerin, L., & Magistretti, P. J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A, 91(22), 10625–10629.
Sánchez-Abarca, L. I., Tabernero, A. & Medina, J. M. (2001). Oligodendrocytes use lactate as a source of energy and as a precursor of lipids. Glia, 36(3), 321–329. https://doi.org/10.1002/glia.1119.
Scandella, V., & Knobloch, M. (2019). Sensing the environment: extracellular lactate levels control adult neurogenesis. Cell Stem Cell, 25(6), 729–731. https://doi.org/10.1016/j.stem.2019.11.008.
Sultan, S., Li, L., Moss, J., Petrelli, F., Cassé, F., Gebara, E., et al. (2015). Synaptic integration of adult-born hippocampal neurons is locally controlled by astrocytes. Neuron, 88(5), 957–972. https://doi.org/10.1016/j.neuron.2015.10.037.
Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., et al. (2011). Astrocyte-neuron lactate transport is required for long-term memory formation. Cell, 144(5), 810–823. https://doi.org/10.1016/j.cell.2011.02.018.
Vezzoli, E., Calì, C., De Roo, M., Ponzoni, L., Sogne, E., Gagnon, N., et al. (2020). Ultrastructural evidence for a role of astrocytes and glycogen-derived lactate in learning-dependent synaptic stabilization. Cerebral Cortex, 30(4), 2114–2127. https://doi.org/10.1093/cercor/bhz226.
Wang, J., Cui, Y., Yu, Z., Wang, W., Cheng, X., Ji, W., et al. (2019). Brain endothelial cells maintain lactate homeostasis and control adult hippocampal neurogenesis. Cell Stem Cell, 25(6), 754-767.e759. https://doi.org/10.1016/j.stem.2019.09.009.
Yang, J., Ruchti, E., Petit, J. M., Jourdain, P., Grenningloh, G., Allaman, I., et al. (2014). Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci U S A, 111(33), 12228–12233. https://doi.org/10.1073/pnas.1322912111.
Zhang, H., Kim, Y., Ro, E. J., Ho, C., Lee, D., Trapp, B. D., et al. (2020). Hippocampal neurogenesis and neural circuit formation in a cuprizone-induced multiple sclerosis mouse model. Journal of Neuroscience, 40(2), 447–458. https://doi.org/10.1523/JNEUROSCI.0866-19.2019.
Zhou, J., Liu, T., Guo, H., Cui, H., Li, P., Feng, D., et al. (2018). Lactate potentiates angiogenesis and neurogenesis in experimental intracerebral hemorrhage. Experimental & Molecular Medicine, 50(7), 78. https://doi.org/10.1038/s12276-018-0113-2.
Acknowledgements
This work was funded by the Paul Feder fund for Alzheimer’s disease research, and the manuscript was edited by Yael Laure.
Funding
This work was funded by the Paul Feder fund for Alzheimer’s disease research.
Author information
Authors and Affiliations
Contributions
RN and EO wrote the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Nicola, R., Okun, E. Adult Hippocampal Neurogenesis: One Lactate to Rule Them All. Neuromol Med 23, 445–448 (2021). https://doi.org/10.1007/s12017-021-08658-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12017-021-08658-y