Current understanding of adult neurogenesis in the mammalian brain: how does adult neurogenesis decrease with age?

Abstract

Adult neurogenesis occurs throughout life in restricted brain regions in mammals. However, the number of neural stem cells (NSCs) that generate new neurons steadily decreases with age, resulting in a decrease in neurogenesis. Transplantation of mesenchymal cells or cultured NSCs has been studied as a promising treatment in models of several brain injuries including cerebral infarction and cerebral contusion. Considering the problems of host-versusgraft reactions and the tumorigenicity of transplanted cells, the mobilization of endogenous adult NSCs should be more feasible for the treatment of these brain injuries. However, the number of adult NSCs in the adult brain is limited, and their mitotic potential is low. Here, we outline what we know to date about why the number of NSCs and adult neurogenesis decrease with age. We also discuss issues applicable to regenerative medicine.

Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods

“…Analysis of cell populations in the hippocampal neurogenic niche using BrdU and DCX labeling ( Figure 1E ) revealed that the number of BrdU + and BrdU + /DCX + cells is reduced in both juvenile and adult AP2γ KO mice, suggesting a decrease in the number of fast proliferating cells (TAPs) and neuroblasts, respectively ( Figure 1F–I ). Of note, we observed a decrease in these cell populations with age in both WT and AP2γ KO mice in agreement with previous reports ( Kase et al, 2020 ; Katsimpardi and Lledo, 2018 ; Supplementary file 1 ).…”

“…Yet, these reduced neurogenesis and delayed maturation did not alter the definitive morphology of granular neurons, another form of hippocampal structural plasticity ( Bessa et al, 2009 ; Mateus-Pinheiro et al, 2013a ). Due to a large amount and density of DCX + cells in the DG of juvenile mice ( Kase et al, 2020 ; Katsimpardi and Lledo, 2018 ), we were unable to analyze their morphology and understand the impact of AP2γ deletion at this period.…”

Constitutive AP2γ deficiency reduces postnatal hippocampal neurogenesis and induces behavioral deficits in juvenile mice that persist during adulthood

“…Analysis of cell populations in the hippocampal neurogenic niche using BrdU and doublecortin (DCX) labelling (Figure 1E) revealed that the number of BrdU + and BrdU + DCX + cells is reduced in both juvenile and adult AP2g +/mice, suggesting a decrease in the number of fast proliferating cells (transient amplifying progenitor cells (TAPs) and neuroblasts, respectively (Figure 1F-I). Of note, we observed a decrease in these cell populations with age in both WT and AP2g +/mice in agreement with previous reports (Kase et al, 2020;Katsimpardi and Lledo, 2018) (BrdU + : Supplementary Figure 1A; BrdU + DCX + : Supplementary Figure 1B). In contrast, and despite an increased length (Supplementary Figure 1C) and neuronal arborization (Supplementary Figure 1D) of DG granular neurons with age, constitutive deficiency of AP2g does not impact neither the dendritic length (Figure 1J-K), nor the neuronal complexity, in both postnatal periods (Supplementary Figure 1D).…”

Telomerase Positive Totipotent Stem Cells and Pluripotent Stem Cells in the Adult Brain I. Cerebral Cortex

“…The model systems studied included integration into neuronal circuits, modification of local microenvironments, local trophic support and protection of regenerating neuronal cells [41][42][43]. Transplantation of bone morrow-derived mesenchymal stem cells and progenitor neural stem cells have demonstrated problems of graft versus host disease response and tumorgenicity of implanted cells, suggesting that other avenues should be considered [44]. An alternative approach to transplantation of exogenous cells for replacing lost neurons due to brain injury would be to reprogram reactive glial cells into functional neurons using direct lineage programming in vivo [45][46][47].…”