http://dukespace.lib.duke.edu/dspace/handle/10161/8778
2014
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2016-05-03
Abstract:
It is commonly accepted that aerobic exercise increases hippocampal
neurogenesis, learning and memory, as well as stress resiliency.
However, human populations are widely variable in their inherent aerobic
fitness as well as their capacity to show increased aerobic fitness
following a period of regimented exercise. It is unclear whether these
inherent or acquired components of aerobic fitness play a role in
neurocognition. To isolate the potential role of inherent aerobic
fitness, we exploited a rat model of high (HCR) and low (LCR) inherent
aerobic capacity for running. At a baseline, HCR rats have two- to
three-fold higher aerobic capacity than LCR rats. We found that HCR rats
also had two- to three- fold more young neurons in the hippocampus than
LCR rats as well as rats from the heterogeneous founder population. We
then asked whether this enhanced neurogenesis translates to enhanced
hippocampal cognition, as is typically seen in exercise-trained animals.
Compared to LCR rats, HCR rats performed with high accuracy on tasks
designed to test neurogenesis-dependent pattern separation ability by
examining investigatory behavior between very similar objects or
locations. To investigate whether an aerobic response to exercise is
required for exercise-induced changes in neurogenesis and cognition, we
utilized a rat model of high (HRT) and low (LRT) aerobic response to
treadmill training. At a baseline, HRT and LRT rats have comparable
aerobic capacity as measured by a standard treadmill fit test, yet after
a standardized training regimen, HRT but not LRT rats robustly increase
their aerobic capacity for running. We found that sedentary LRT and HRT
rats had equivalent levels of hippocampal neurogenesis, but only HRT
rats had an elevation in the number of young neurons in the hippocampus
following training, which was positively correlated with accuracy on
pattern separation tasks. Taken together, these data suggest that a
significant elevation in aerobic capacity is necessary for
exercise-induced hippocampal neurogenesis and hippocampal
neurogenesis-dependent learning and memory. To investigate the potential
for high aerobic capacity to be neuroprotective, doxorubicin
chemotherapy was administered to LCR and HCR rats. While doxorubicin
induces a progressive decrease in aerobic capacity as well as
neurogenesis, HCR rats remain at higher levels on those measures
compared to even saline-treated LCR rats. HCR and LCR rats that received
exercise training throughout doxorubicin treatment demonstrated
positive effects of exercise on aerobic capacity and neurogenesis,
regardless of inherent aerobic capacity. Overall, these findings
demonstrate that inherent and acquired components of aerobic fitness
play a crucial role not only in the cardiorespiratory system but also
the fitness of the brain.
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