Abstract
Enhanced mental and physical activity can have positive effects on the function of aging brain, both in the experimental animals and human patients, although cellular mechanisms underlying these effects are currently unclear. There is a growing evidence that pre-clinical stage of many neurodegenerative diseases involves changes in interactions between astrocytes and neurons. Conversely, astrocytes are strategically positioned to mediate the positive influence of physical activity and diet on neuronal function. Thus, development of therapeutic agents which could improve the astroglia-neuron communications in ageing brain is of crucial importance. Recent advances in studies of cellular mechanisms of brain longevity suggest that astrocyte-neuron communications have a vital role in the beneficial effects of caloric restriction, physical exercise and their pharmacological mimetics on synaptic homeostasis and cognitive function. In particular, our recent data indicate that noradrenaline uptake inhibitor atomoxetine can enhance astrocytic Ca2+-signaling and astroglia-driven modulation of synaptic plasticity. Similar effects were exhibited by caloric restriction-mimetics metformin and resveratrol. The emerged data also suggest that astrocytes could be involved in the modulatory action of caloric restriction and its mimetics on neuronal autophagy. Still, the efficiency of astrocyte-targeting compounds in preventing age-related cognitive decline is yet to be fully explored, in particular in the animal models of neurodegenerative diseases and autophagy impairment.
Highlights
Due to changing demographics, age-related cognitive decline and neurological disorders have become a real medical and societal problem
Recent data [5, 7] show that environmental enrichment (EE) and caloric restriction (CR) can ameliorate the aging-related alterations in synaptic transmission and mitigate the age-related decline in synaptic plasticity in the neocortical neurons
CR was able to rescue the long-term synaptic plasticity in neocortical neurons of old wild-type mice [5, 7]. These beneficial effects are mediated by astrocytes because (1) CR enhanced astroglial Ca2+ signalling and release of gliotransmitters such as ATP and D-Serine [5, 28]; (2) beneficial effects of CR were strongly attenuated in the dnSNARE mice with selective impairment of astroglial exocytosis [5, 28]
Summary
Age-related cognitive decline and neurological disorders have become a real medical and societal problem. A growing evidence of beneficial effects of exercise and diet on brain function gave rise to a concept of “cognitive reserve”-a set of cellular and molecular mechanisms which allow the brain to adapt to age-related pathologies despite underlying neural changes [8]. This concept is attractive in view of necessity to develop pharmaceutical agents for prevention/amelioration of cognitive decline [3, 8,9,10,11]. In this article we overview the emerging evidence of importance for astrocytes in the mechanisms of cognitive reserve which render astroglia a perspective target for CRand exercise mimetics
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