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.
Highlights
Environmental enrichment (EE) is considered as an environment with numerous sensorimotor, cognitive, and social stimulations able to affect brain plasticity, to restore brain functional reserves, and to facilitate establishment of novel connections actual for preventive or rehabilitation strategies
Immunohistochemical analysis of molecular markers expression in cells at different stages of neurogenesis (Pax6, Neurogenin 2, NeuroD1, NeuN) in the hippocampus revealed that their levels were dramatically affected in amyloid β (Aβ)-treated rats and in the group of aging animals (Figures 1A–D)
Expression of Pax6 was efficiently restored by EE in all the groups tested (Figure 2). It is well-known that Pax6 is a transcription factor controlling proliferation of multipotent stem/progenitor cells in hippocampus and cortex being predominantly expressed by radial glia
Summary
Environmental enrichment (EE) is considered as an environment with numerous sensorimotor, cognitive, and social stimulations able to affect brain plasticity, to restore brain functional reserves, and to facilitate establishment of novel connections actual for preventive or rehabilitation strategies. EE stimulates neurogenesis and synapse turnover, integration of newly-formed cells into neuronal ensembles, modifies epigenetic mechanisms controlling resistance to oxidative stress, modulates production of neurotransmitters and molecules with neurotrophic activity, prevents apoptosis, suppresses neuroinflammation, affects neuron-glia interactions, thereby enhancing cognition, learning, and social communications in animals or humans with or without brain pathology (Herring et al, 2011; Cotel et al, 2012; Komleva Iu et al, 2013; Leger et al, 2015; Grinan-Ferre et al, 2016; Stuart et al, 2017) These effects well-correspond to those observed in people practicing so-called cognitive training because of their professional duties or personal habits and demonstrating good preservation of cognitive functions even at the eldest period of life (Mora, 2013). Prevention or treatment of Alzheimer-type neurodegeneration is one of the most challenging questions in the modern neuroscience which is directly linked to the controlled modulation of hippocampal plasticity (Balietti et al, 2012) In such context, EE provides a lot of premises for its effective application: prevention of hippocampal astroglial dysfunction in the AD transgenic mice (Rodriguez et al, 2013), up-regulation of brain-derived growth factor expression in the hippocampus of senescenceaccelerated prone mice (Yuan et al, 2012), prevention of amyloid β (Aβ) deposition and memory impairment in AD model mice (Maesako et al, 2012), modulation of hippocampal synaptic proteins expression (Barak et al, 2013)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
