Age-Dependent Remarkable Regenerative Potential of the Dentate Gyrus Provided by Intrinsic Stem Cells

Abstract

Multiple insults to the brain lead to neuronal cell death, thus raising the question to what extent can lost neurons be replenished by adult neurogenesis. Here we focused on the hippocampus and especially the dentate gyrus (DG), a vulnerable brain region and one of the two sites where adult neuronal stem cells (NSCs) reside. While adult hippocampal neurogenesis was extensively studied with regard to its contribution to cognitive enhancement, we focused on their underestimated capability to repair a massively injured, nonfunctional DG. To address this issue, we inflicted substantial DG-specific damage in mice of either sex either by diphtheria toxin-based ablation of Ͼ50% of mature DG granule cells (GCs) or by prolonged brain-specific VEGF overexpression culminating in extensive, highly selective loss of DG GCs (thereby also reinforcing the notion of selective DG vulnerability). The neurogenic system promoted effective regeneration by increasing NSCs proliferation/survival rates, restoring a nearly original DG mass, promoting proper rewiring of regenerated neurons to their afferent and efferent partners, and regaining of lost spatial memory. Notably, concomitantly with the natural age-related decline in the levels of neurogenesis, the regenerative capacity of the hippocampus also subsided with age. The study thus revealed an unappreciated regenerative potential of the young DG and suggests hippocampal NSCs as a critical reservoir enabling recovery from catastrophic DG damage.

Effect of caffeinated energy drinks on the structure of hippocampal cornu ammonis 1 and dentate gyrus of adult male albino rats

“…Hippocampal CA1 is one of three brain regions considered most susceptible to oxidative stress and various insults leading to rapid decline in its function [21,22]. Also, the DG, is another vulnerable brain tissue that contains adult neuronal stem cells which are responsible for adult hippocampal neurogenesis [23]. Caffeinated energy drinks are available worldwide and are frequently used to improve mood, physical performance and reduce mental fatigue [4,5].…”

“…In addition, it is one of three brain regions that are most susceptible to oxidative stress and the first to undergo decline in its function [22]. The dentate gyrus (DG), is another vulnerable brain tissue that contains adult neuronal stem cells which are responsible for adult hippocampal neurogenesis [23].…”

Therapeutic Plasticity of Neural Stem Cells

“…Depending on the type and concentration, they strengthen or weaken synaptic morphology (141) and synaptic responses (142), leading to long-term potentiation (LTP) or long-term depression (LTD). Moreover, they can form new connections and pathways and can change the wiring of the circuits (143). In severe pathological conditions, physiological trophic effects will not provide sufficient tissue regeneration.…”

GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

“…The newly generated granular neurons in the DG region of the hippocampus are functionally integrated into the hippocampal circuit at 4 weeks [ 27 ]. Furthermore, the DG region is thought to play an essential role in learning, memory, and spatial navigation tasks [ 46 ], and previous studies demonstrated that neurogenesis in the DG region of the hippocampus can rescue the ability of learning and memory [ 33 , 51 , 52 ]. Our further study found that the number of BrdU + /NeuN + cells increased significantly on day 28, indicating that the number of newborn cells that survived and differentiated into neurons increased.…”