Selenium mediates the exercise-induced increase in adult hippocampal neurogenesis
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Selenium increases hippocampal precursor proliferation and adult neurogenesis
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Selenium reverses cognitive decline in aging and in hippocampal injury
Summary
Although the neurogenesis-enhancing effects of exercise have been extensively studied, the molecular mechanisms underlying this response remain unclear. Here, we propose that this is mediated by the exercise-induced systemic release of the antioxidant selenium transport protein, selenoprotein P (SEPP1). Using knockout mouse models, we confirmed that SEPP1 and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) are required for the exercise-induced increase in adult hippocampal neurogenesis. In vivo selenium infusion increased hippocampal neural precursor cell (NPC) proliferation and adult neurogenesis. Mimicking the effect of exercise through dietary selenium supplementation restored neurogenesis and reversed the cognitive decline associated with aging and hippocampal injury, suggesting potential therapeutic relevance. These results provide a molecular mechanism linking exercise-induced changes in the systemic environment to the activation of quiescent hippocampal NPCs and their subsequent recruitment into the neurogenic trajectory.
Graphical abstract
Keywords
adult neurogenesis
hippocampus
selenium
dentate gyrus
exercise
neural precursor cell
neural stem cell
aging
endothelin-1
hippocampal lesion
Data and code availability
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The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2019) partner repository with the dataset identifier PXD027324. All values used to generate the graphs of the paper can be found in the file Data S1.
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This study did not generate any code.
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Any additional information required to reanalyze the data reported in this paper. Is available from the lead contact upon request.
Present address: Pharmaceutical Research and Early Development, Ocular Technologies, I2O, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland