Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain |
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Authors: | Evelin L Schaeffer Barbara A NovaesEmanuelle R da Silva Heni D SkafÁlvaro G Mendes-Neto |
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Institution: | Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010, Sao Paulo, SP, Brazil |
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Abstract: | Adult neurogenesis occurs in the subgranular zone (SGZ) and subventricular zone (SVZ). New SGZ neurons migrate into the granule cell layer of the dentate gyrus (DG). New SVZ neurons seem to enter the association neocortex and entorhinal cortex besides the olfactory bulb. Alzheimer disease (AD) is characterized by neuron loss in the hippocampus (DG and CA1 field), entorhinal cortex, and association neocortex, which underlies the learning and memory deficits. We hypothesized that, if the AD brain can support neurogenesis, strategies to stimulate the neurogenesis process could have therapeutic value in AD. We reviewed the literature on: (a) the functional significance of adult-born neurons; (b) the occurrence of endogenous neurogenesis in AD; and (c) strategies to stimulate the adult neurogenesis process. We found that: (a) new neurons in the adult DG contribute to memory function; (b) new neurons are generated in the SGZ and SVZ of AD brains, but they fail to differentiate into mature neurons in the target regions; and (c) numerous strategies (Lithium, Glatiramer Acetate, nerve growth factor, environmental enrichment) can enhance adult neurogenesis and promote maturation of newly generated neurons. Such strategies might help to compensate for the loss of neurons and improve the memory function in AD. |
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Keywords: | Aβ β-amyloid AD Alzheimer disease APP amyloid precursor protein BDNF brain-derived neurotrophic factor BrdU bromodeoxyuridine CA cornu ammonis DCX doublecortin DG dentate gyrus EGF epidermal growth factor FGF fibroblast growth factor GCL granule cell layer GFAP glial fibrillary acidic protein MAP microtubule-associated protein MCI mild cognitive impairment MCM2 mini-chromosome maintenance protein 2 NeuN Neuronal Nuclei NeuroD neurogenic differentiation factor NGF nerve growth factor NPC neural progenitor cell NSC neural stem cell PS Presenilin PSA-NCAM polysialylated neural cell adhesion molecule SGZ subgranular zone SVZ subventricular zone TUC-4 division/Ulip-1/CRMP-4 |
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