Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb

Abstract

Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and olfactory bulbs continues into adulthood and has been implicated in the cognitive function of the adult brain. The basal forebrain cholinergic system has been suggested to play a role in regulating neurogenesis as well as learning and memory in these regions. Herein, we report that highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive immature cells as well as neuronal nuclei (NeuN)-positive mature neurons in the dentate gyrus and olfactory bulb express multiple acetylcholine receptor subunits and make contact with cholinergic fibers. To examine the function of acetylcholine in neurogenesis, we used donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that improves cognitive impairment in Alzheimer's disease. Intraperitoneal administrations of donepezil significantly enhanced the survival of newborn neurons, but not proliferation of neural progenitor cells in the subgranular zone or the subventricular zone of normal mice. Moreover, donepezil treatment reversed the chronic stress-induced decrease in neurogenesis. Taken together, these results suggest that activation of the cholinergic system promotes survival of newborn neurons in the adult dentate gyrus and olfactory bulb under both normal and stressed conditions.

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

“…In LM11A-31-treated samples, the numbers of BrdU cells are significantly increased, while the percentage of cells that are also NeuN1 is significantly less than in the sham-vehicle group, although resulting in numbers of double-labeled cells greater than sham and more than twofold higher than that seen in injury/vehicle. n 5 4/group; *, p < .05; **, p < .01; and ***, expressing fibers (likely type II cholinergic fibers derived from neurons in the medial septal nuclei of the basal forebrain [49,56,57]). In addition, this cell population exhibits neurotrophic responses to cholinergic activity [49].…”

“…n 5 4/group; *, p < .05; **, p < .01; and ***, expressing fibers (likely type II cholinergic fibers derived from neurons in the medial septal nuclei of the basal forebrain [49,56,57]). In addition, this cell population exhibits neurotrophic responses to cholinergic activity [49]. These observations, together with findings that genetic p75 NTR modulation and LM11A-31 support the integrity of neurites of injured basal forebrain/cholinergic neurons [4,33,36], suggest the possibility of indirect compound effects through cholinergic fiber function.…”

“…4C). p75 NTR and PSA-NCAM did not extensively colocalize, although there were small areas of signal coincidence which could represent coexpression in PSA-NCAM-expressing subgranular progenitor cells or close contacts between cholinergic fibers and progenitor cells (as described by Kaneko et al [49]) (Fig. 4A, Supporting Information Fig.…”

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

“…It is also conceivable that various functionally divergent subpopulations of microglia exist, some having pro-, others antineurogenic effects (Ekdahl et al 2009). Specific subsets of cytokines can even be proneurogenic although others decrease neurogenesis through interleukin (IL)-1b (Kaneko et al 2006;Zunszain et al 2012). Proinflammatory mediators can further restrict neurogenesis (Iosif et al 2006).…”

Effects of Treadmill Exercise on Memory, Hippocampal Cell Proliferation, BDNF, TrkB, and Forebrain Cholinergic Cells in Adolescent Rats

“…따라서 중격 콜린신경의 활성은 해마 BDNF 발현의 증가 [29], 신경세포 생성 [22]과 생존 [20]을 향상시켰다. 반대로 콜린 신경의 손상은 BDNF 발현 [7]과 신경세포 생성 [9]을 감소 시켰다.…”