Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)408-423.e1-e8
Number of pages25
JournalCell metabolism
Issue number3
Publication statusPublished - 1 Mar 2022

External IDs

PubMed 35120590
WOS 000764898700007
Mendeley 24d41184-d6a0-3330-b9c6-5ce749e6e83f
ORCID /0000-0002-5304-4061/work/142238790


Research priority areas of TU Dresden

Sustainable Development Goals


  • Brain, Dentate gyrus, Gene-expression, Increases, Neural stem-cells, Neurons, Precursors, Ros, Selenoprotein-p, Synaptic plasticity, Cell Proliferation, Selenium/metabolism, Animals, Neural Stem Cells/metabolism, Neurogenesis/physiology, Aging, Mice, Hippocampus, neural stem cell, exercise, neural precursor cell, selenium, endothelin-1, adult neurogenesis, hippocampus, dentate gyrus, aging, hippocampal lesion