Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis

Abstract

Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the "brain cognitive reserve", that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging.

Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome

“…In addition, phagocytosis of newborn cells has also been recently shown to play a role in sculpting sex differences in the developing amygdala (VanRyzin et al, 2019). While previous work has suggested a largely detrimental effect of microglia on hippocampal neurogenesis (Valero et al, 2016), our data are in agreement with recent evidences supporting the essential role of macrophages and other immune cells in remodeling stem cells niches (Naik et al, 2018).…”

The Indispensable Roles of Microglia and Astrocytes during Brain Development

“…Interestingly, apart from their effect on developmental neurogenesis, microglia can influence adult hippocampal neurogenesis by phagocytosis of apoptotic cells (Sierra et al, 2010) and are also able to provide trophic support to new adult born neurons in the hippocampus and SVZ (for review see Gemma and Bachstetter, 2013; Ribeiro Xavier et al, 2015). It is thus likely that the mechanisms microglia use to affect developmental neuro- and astrogenesis, can also be used to influence SVZ and hippocampal neurogenesis in the adult (Aarum et al, 2003; Kanski et al, 2014; Valero et al, 2016). …”

CX3CR1 modulates cognitive dysfunction induced by sleep deprivation

“…It is believed that the binding of soluble CX3CL1 to its receptor CX3CR1 maintains the "synapse pruning" function of microglia [43]. A previous study found that the number of microglia and dendritic spine density increased in CX3CR1-knockout mice at the age of 2-3 weeks.…”