Abstract
Thiamine (vitamin B1) is co-factor for three pivotal enzymes for glycolytic metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Thiamine deficiency leads to neurodegeneration of several brain regions, especially the cerebellum. In addition, several neurodegenerative diseases are associated with impairments of glycolytic metabolism, including Alzheimer’s disease. Therefore, understanding the link between dysfunction of the glycolytic pathway and neuronal death will be an important step to comprehend the mechanism and progression of neuronal degeneration as well as the development of new treatment for neurodegenerative states. Here, using an in vitro model to study the effects of thiamine deficiency on cerebellum granule neurons, we show an increase in Ca2+ current density and CaV1.2 expression. These results indicate a link between alterations in glycolytic metabolism and changes to Ca2+ dynamics, two factors that have been implicated in neurodegeneration.
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Acknowledgments
This study was funded by São Paulo Research Foundation (FAPESP), Project Number 2012/50336-2 to FAO. DCML held a scholarship from Coordination for the Improvement of Higher Education Personnel (CAPES). C. Kushmerick and J.S. Cruz were funded by CNPq (The National Council for Scientific and Technological Development) research fellowships.
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Moreira-Lobo, D.C., Cruz, J.S., Silva, F.R. et al. Thiamine Deficiency Increases Ca2+ Current and CaV1.2 L-type Ca2+ Channel Levels in Cerebellum Granular Neurons. Cell Mol Neurobiol 37, 453–460 (2017). https://doi.org/10.1007/s10571-016-0378-8
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DOI: https://doi.org/10.1007/s10571-016-0378-8