Abstract
There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging wild-type (WT) mice has not yet been studied in detail. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE) paradigm for a duration of 11 months, leads to reduced anxiety and improved spatial reference memory in C57BL6 WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH) and EE mice, the number of dentate gyrus (DG) neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders.
Highlights
Given the fact that no effective drugs to treat dementia disorders are available to date, the research focus has more and more shifted toward more promising preventive approaches in recent years
Mice maintained under EE conditions spent significantly more time in the center region when compared to sedentary controls (p < 0.05; Figure 2A), indicating a loss of anxiety
Spatial reference memory was assessed in standard and enriched housed WT mice using the Morris water maze (MWM) task. 12-monthold WT mice housed under standard housed (SH) and EE conditions showed progressively decreased escape latencies over 3 days of cued training as expected (Figure 3A), while no differences in swimming speed were detected (Figure 3D)
Summary
Given the fact that no effective drugs to treat dementia disorders are available to date, the research focus has more and more shifted toward more promising preventive approaches in recent years. A recently published 29-years-long follow-up study with a Finnish twin cohort disclosed that long-term vigorous physical activity during adulthood significantly decreases the risk to develop dementia. Proposed mechanisms disclosing how physical activity lowers the risk of dementia in humans are diverse and include enhanced cerebral blood flow as well as synthesis of neurotransmitters among others (Coelho et al, 2014). It has been reported that higher levels of aerobic exercise are associated with an increased hippocampal volume and improved spatial memory in older subjects (Erickson et al, 2011) and that physical activity reduces hippocampal atrophy in individuals at genetic risk for AD (Smith et al, 2014)
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