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

Abstract

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 in vivo and neurosphere-forming capacity of hippocampal stem/progenitor cells in vitro. 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 in vitro 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 in vivo, EE was almost ineffective in the recovery of hippocampal neurogenic reserve in vitro 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.

Effects and Mechanism of Action of Neonatal Versus Adult Astrocytes on Neural Stem Cell Proliferation After Traumatic Brain Injury

“…It is well known that the ability of NSCs to proliferate and differentiate depends largely on the neuro‐microenvironment . An increasing number of studies have shown that, with age, the neuro‐microenvironment under physiological or pathological conditions differs significantly . The CNS is composed of different types of nerve cells which interact with each other to form a precise and complex neural network .…”

Environmental enrichment improves cognitive symptoms and pathological features in a focal model of cortical damage of multiple sclerosis

“…Exposure to EE has demonstrated to improve the course of aging as well as neurodegenerative diseases including traumatic brain injury, perinatal asphyxia, Huntington's, Parkinson´s and Alzheimer's diseases (Birch and Kelly, 2019;Fischer, 2016;Frasca et al, 2013;Galeano et al, 2014;Goncalves et al, 2018;Jungling et al, 2017;Mo et al, 2015;Pang and Hannan, 2013;Ziegler-Waldkirch et al, 2018). Recent studies using animal models of Huntington's disease (Mo et al, 2015;Steventon et al, 2015), Alzheimer's disease (Prado Lima et al, 2018;Salmin et al, 2017) and Parkinson's disease (Jungling et al, 2017) provide increasing evidence of neuroprotection in these pathologies with behavioural, cellular and molecular changes induced by EE. Thus, environmental factors could impact on the function of the immune system within the brain and may represent a non-pharmacological agent that could be useful as a complementary tool to the pharmacological treatment used in MS and other neurological diseases.…”

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

“…Probably, the most reliable way to get an NVU/BBB model resembling properties of aging brain tissue might be in obtaining of cells from the aged animal followed by their growth in vitro within the multi-cellular ensemble (endothelial cells and perivascular cells) mimicking NVU microenvironment. However, this approach is difficult to execute because proliferation and establishment of appropriate and functionally competent intercellular contacts are very limited in the culture of cells isolated from the aged brain tissue (Salmin et al, 2017 ). But very recent findings suggest that neurogenic potential of cells in physiological aging might be well preserved (Boldrini et al, 2018 ).…”