Review Advance Articles

Vitamin D deficiency as a potential risk factor for accelerated aging, impaired hippocampal neurogenesis and cognitive decline: a role for Wnt/β-catenin signaling

Figure 4. Hypothetical role of vitamin D in facilitating the activation of quiescent neural stem cells (qNSC) in the aged brain and its consequences in cognitive impairment. The effects of vitamin D on cognitive decline might be mediated by its capacity to stimulate neurogenesis in the old neurogenic niche. Several factors such as inflammation, and Wnt signaling inhibition facilitate the state of quiescence in NSC diminishing the neurogenic rate [78, 80]. High NSC-Wnt activity leads to longer time in quiescence while enhancing the probability of activation [114]. Vitamin D may activate canonical Wnt signaling through the repression of Wnt inhibitors such as DKK1 and prolonging the time NSC spend in quiescence, increasing their probability to be activated and avoiding being depleted via their differentiation towards astroglial cells [114]. It may be possible that a deficiency in vitamin D results in Wnt signaling imbalance, impairing the gradual activation of NSC required to maintain a neurogenic rate. Thus, hypovitaminosis D might impair these mechanisms leading to a reduction in neurogenesis resulting in cognitive decline.