Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis

Abstract

Adult hippocampal neurogenesis is important for preserving learning and memory-related cognitive functions. Physical exercise, especially voluntary running, is one of the strongest stimuli to promote neurogenesis and has beneficial effects on cognitive functions. Voluntary running promotes exit of neural stem cells (NSCs) from the quiescent stage, proliferation of NSCs and progenitors, survival of newborn cells, morphological development of immature neuron, and integration of new neurons into the hippocampal circuitry. However, the detailed mechanisms driving these changes remain unclear. In this review, we will summarize current knowledge with respect to molecular mechanisms underlying voluntary running-induced neurogenesis, highlighting recent genome-wide gene expression analyses. In addition, we will discuss new approaches and future directions for dissecting the complex cellular mechanisms driving change in adult-born new neurons in response to physical exercise.

Keywords: adult neurogenesis; gene expression; genome wide; physical exercise; voluntary running.

Figure 1.. Factors that promote and inhibit adult hippocampal neurogenesis

The summary of negative factors that inhibit adult hippocampal neurogenesis (black) and positive factors that promote adult hippocampal neurogenesis (white) is based on extensive literature [see relevant reviews: (Bieri et al., 2023; Cooper et al., 2018; Kempermann, 2022; Kempermann et al., 2015; Zocher and Toda, 2023)

Figure. 2. Voluntary running has positive impact on all developmental stages of new neurons during adult hippocampal neurogenesis:

Voluntary running activates quiescent NSCs (Dong et al., 2019; Lugert et al., 2010; Wang et al., 2011), leads to increased NSC and IPC proliferation: (Farioli-Vecchioli et al., 2014; Overall et al., 2016; van Praag et al., 1999), enhances differentiation, survival of newborn immature neurons (van Praag et al., 2005; Vivar et al., 2016), promotes migration and maturation of new neurons (Gao et al., 2020; Piatti et al., 2011; Steib et al., 2014; Zhao et al., 2006), improves dendritic spine formation (Zhao et al., 2014), circuit integration (Vivar et al., 2016), and synaptic plasticity (Schmidt-Hieber et al., 2004) of new neurons.