Differential Roles of Environmental Enrichment in Alzheimer's Type of Neurodegeneration and Physiological Aging

• Published in: Frontiers in aging neuroscience Vol. 9; p. 245
• Main Authors: Salmin, Vladimir V, Komleva, Yulia K, Kuvacheva, Natalia V, Morgun, Andrey V, Khilazheva, Elena D, Lopatina, Olga L, Pozhilenkova, Elena A, Shapovalov, Konstantin A, Uspenskaya, Yulia A, Salmina, Alla B
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 26.07.2017; Frontiers Media S.A
• Subjects: Aging; Alzheimer’s disease; Beta2 protein; Brain stem; Cell culture; Cell differentiation; Cell proliferation; Comparative analysis; Enrichment; environmental enrichment; Epigenetics; Hippocampus; Mathematical models; Neural stem cells; Neurodegeneration; Neurodegenerative diseases; Neurodevelopmental disorders; Neurogenesis; Neuroprotection; Neuroscience; Neurosciences; neurosphere; Oxidative stress; Pathology; Pax6 protein; Physiology; Progenitor cells; Senescence; Stem cell transplantation; Stem cells; time-lag model; Russia; environmental enrichment; neurogenesis; aging; Alzheimer’s disease; time-lag model; neurosphere
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2017.00245

Impairment of hippocampal adult neurogenesis in aging or degenerating brain is a well-known phenomenon caused by the shortage of brain stem cell pool, alterations in the local microenvironment within the neurogenic niches, or deregulation of stem cell development. Environmental enrichment (EE) has been proposed as a potent tool to restore brain functions, to prevent aging-associated neurodegeneration, and to cure neuronal deficits seen in neurodevelopmental and neurodegenerative disorders. Here, we report our data on the effects of environmental enrichment on hippocampal neurogenesis and neurosphere-forming capacity of hippocampal stem/progenitor cells Two models - Alzheimer's type of neurodegeneration and physiological brain aging - were chosen for the comparative analysis of EE effects. We found that environmental enrichment greatly affects the expression of markers specific for stem cells, progenitor cells and differentiated neurons (Pax6, Ngn2, NeuroD1, NeuN) in the hippocampus of young adult rats or rats with Alzheimer's disease (AD) model but less efficiently in aged animals. Application of time-lag mathematical model for the analysis of impedance traces obtained in real-time monitoring of cell proliferation revealed that EE could restore neurosphere-forming capacity of hippocampal stem/progenitor cells more efficiently in young adult animals (fourfold greater in the control group comparing to the AD model group) but not in the aged rats (no positive effect of environmental enrichment at all). In accordance with the results obtained , EE was almost ineffective in the recovery of hippocampal neurogenic reserve in aged, but not in amyloid-treated or young adult, rats. Therefore, EE-based neuroprotective strategies effective in Aβ-affected brain could not be directly extrapolated to aged brain.