Environmental Enrichment Induces Behavioral Recovery and Enhanced Hippocampal Cell Proliferation in an Antidepressant-Resistant Animal Model for PTSD

Background: Post traumatic stress disorder (PTSD) can be considered the result of a failure to recover after a traumatic experience. Here we studied possible protective and therapeutic aspects of environmental enrichment (with and without a running wheel) in Sprague Dawley rats exposed to an inescapable foot shock procedure (IFS). Methodology/Principal Findings: IFS induced long-lasting contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10 weeks after IFS the rats showed reduced locomotion in an open field. The antidepressants imipramine and escitalopram did not improve anxiogenic behavior following IFS. Also the histone deacetylase (HDAC) inhibitor sodium butyrate did not alleviate the IFS induced immobility. While environmental enrichment (EE) starting two weeks before IFS did not protect the animals from the behavioral effects of the shocks, exposure to EE either immediately after the shock or one week later induced complete recovery three weeks after IFS. In the next set of experiments a running wheel was added to the EE to enable voluntary exercise (EE/VE). This also led to reduced anxiety. Importantly, this behavioral recovery was not due to a loss of memory for the traumatic experience. The behavioral recovery correlated with an increase in cell proliferation in hippocampus, a decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in prefrontal cortex and hippocampus. Conclusions/Significance: This animal study shows the importance of (physical) exercise in the treatment of psychiatri

Does physical activity reduce risk for Alzheimer’s disease through interaction with the stress neuroendocrine system?

Lack of physical activity (PA) is a risk factor for Alzheimer's disease (AD) and PA interventions are believed to provide an effective non-pharmacological approach for attenuating the symptoms of this disease. However, the mechanism of action of these positive effects is currently unknown. It is possible that the benefits may be at least partially mediated by effects on the neuroendocrine stress system. Chronic stress can lead to dysfunction of the hypothalamic pituitary adrenal (HPA) axis, leading to aberrant basal and circadian patterns of cortisol secretion and a cascade of negative downstream events. These factors have been linked not only to reduced cognitive function in the non-demented but also increased levels of Amyloid β plaques and protein Tau "tangles" (the neuropathological hallmarks of AD) in mouse models of this disease. However, there is evidence that PA can have restorative effects on the stress neuroendocrine system and related risk factors relevant to AD. We explore the possibility that PA can positively impact upon AD by restoring normative HPA axis function, with consequent downstream effects upon underlying neuropathology and associated cognitive function. We conclude with suggestions for future research to test this hypothesis in patients with AD