Influence of hippocampal niche signals on neural stem cell functions during aging

Abstract

The genesis of new neurons from neural stem cells in the adult brain offers the hope that this mechanism of plasticity can be harnessed for the treatment of brain injuries and diseases. However, neurogenesis becomes impaired during the normal course of aging; this is also the primary risk factor for most neurodegenerative diseases. The local microenvironment that regulates the function of resident neural stem cells (the "neurogenic niche") is a particularly complex network of various signaling mechanisms, rendering it especially challenging for the dissection of the control of these cells but offering the potential for the advancement of our understanding of the regulation/misregulation of neurogenesis. In this review, we examine the factors that control neurogenesis in an age-dependent manner, and we define these signals by the extrinsic mechanism through which they are presented to the neural stem cells. Secreted signals, cell-contact-dependent signals, and extracellular matrix cues all contribute to the regulation of the aging neurogenic niche and offer points of therapeutic intervention.

The impact of age on number and distribution of proliferating cells in subgranular zone in adult mouse brain

“…The decrease of hippocampal neurogenesis in rats with age was noticed by Dr. Joseph Altman in 1965 (Altman and Das, 1965). Later this decrease was reported in many other mammalian species (Seki and Arai, 1995; Kuhn et al, 1996; Drapeau and Nora Abrous, 2008; Morgenstern et al, 2008; Lee et al, 2012; Apple et al, 2017; Mosher and Schaffer, 2017; Smith et al, 2017). Despite many reports of the decline of neurogenesis with age, there is no published detailed analysis of the age effect on neurogenesis in the SGZ in mice (Table 1 in (Drapeau and Nora Abrous, 2008)) similar to what is presented in our study.…”

Impaired adult hippocampal neurogenesis in Alzheimer’s disease is mediated by microRNA-132 deficiency and can be restored by microRNA-132 replacement

“…We show that the running-induced miR-132 upregulation in the hippocampal neurogenic niche becomes compromised with pathology progression, independently of gender, and that these alterations are paralleled by decreased neurogenic potential. The hippocampal neurogenic niche involves a complex network of intercellular communication and molecular regulatory signals, which is receptive to extrinsic and intrinsic cues, such as experience, exercise, aging and increased neuroinflammation (Fuster-Matanzo et al, 2013; Mosher and Schaffer, 2018; Villeda et al, 2011). Our data demonstrate that treatment of human neuronal precursor cells with oligomeric Aβ reduces proliferation and miR-132 expression, consistently with several lines of evidence suggesting that Aβ per se impacts the neurogenic potential of neural stem cells and progenitors (Haughey et al, 2002; He et al, 2013; Lee et al, 2013).…”

High‐throughput combinatorial screening reveals interactions between signaling molecules that regulate adult neural stem cell fate

“…These studies quantitatively demonstrate that a highly intricate and sensitive balance of multiple cues guides the endpoint phenotype of NSC populations and these in vitro results are potentially representative of NSC fate within the adult hippocampal niche. Disruption of precise balances between molecular cues could contribute to the cell and tissue degeneration in the hippocampus during aging (Mosher & Schaffer, 2018) or by disease, having consequences for learning and memory throughout adulthood.…”