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

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.

Author Correction: Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions.

There is growing evidence that both peripheral and resident immune cells play an important part in regulating adult neural stem cell proliferation and neurogenesis, although the contribution of the various immune cell types is still unclear. Mast cells, a population of immune cells known for their role in the allergic response, have been implicated in the regulation of adult hippocampal neurogenesis. Mast cell-deficient c-kitW-sh/W-sh mice have previously been shown to exhibit significantly decreased adult hippocampal neurogenesis and associated learning and memory deficits. However, given that numerous other cell types also express high levels of c-kit, the utility of these mice as a reliable model of mast cell-specific depletion is questionable. We show here, using a different model of mast cell deficiency (Mcpt5CreR26DTA/DTA), that precursor proliferation and adult neurogenesis are not influenced by mast cells in vivo. Interestingly, when applied at supraphysiological doses, mast cells can activate latent hippocampal precursor cells and increase subventricular zone precursor proliferation in vitro, an effect that can be blocked with specific histamine-receptor antagonists. Thus, we conclude that while both mast cells and their major chemical mediator histamine have the potential to affect neural precursor proliferation and neurogenesis, this is unlikely to occur under physiological conditions.