Running exercise mitigates the negative consequences of chronic stress on dorsal hippocampal long-term potentiation in male mice

Abstract

In the hippocampus, learning and memory are likely mediated by synaptic plasticity, known as long-term potentiation (LTP). While chronic intermittent stress is negatively correlated, and exercise positively correlated to LTP induction, we examined whether exercise could mitigate the negative consequences of stress on LTP when co-occurring with stress. Mice were divided into four groups: sedentary no stress, exercise no stress, exercise with stress, and sedentary with stress. Field electrophysiology performed on brain slices confirmed that stress alone significantly reduced dorsal CA1 hippocampal LTP and exercise alone increased LTP compared to controls. Exercise with stress mice exhibited LTP that was significantly greater than mice undergoing stress alone but were not different from sedentary no stress mice. An ELISA illustrated increased corticosterone in stressed mice compared to no stress mice. In addition, a radial arm maze was used to examine behavioral changes in memory during 6 weeks of stress and/or exercise. Exercised mice groups made fewer errors in week 2. RT-qPCR was used to examine the mRNA expression of components in the stress and exercise pathways in the four groups. Significant changes in the expression of the following targets were detected: BDNF, TrkB, glucocorticoid, mineralocorticoid, and dopamine 5 receptors. Collectively, exercise can mitigate some of the negative impact stress has on hippocampal function when both occur concurrently.

Rats bred for high anxiety exhibit distinct fear‐related coping behavior, hippocampal physiology, and synaptic plasticity‐related gene expression

“…The lack of change in the E/I ratio suggests no significant difference in basal glutamatergic or GABAergic input onto CA1 pyramidal cells between HR and LR males. Previous studies show that stress does not change presynaptic release probability in area CA1 in hippocampus (Miller et al, ; Shors & Thompson, ), and we report no differences in PPR, consistent with no change in presynaptic function.…”

“…Changes in long‐term plasticity, a cellular mechanism involved in learning and memory, have been observed after stressful events (Miller et al, ; Shors & Thompson, ; Shors, Weiss, & Thompson, ). We therefore investigated potential HR/LR phenotypic differences in synaptic plasticity, initially via theta burst stimulation (TBS)‐induced LTP, which is dependent on NMDARs (Morgan & Teyler, ) and BDNF (Aarse, Herlitze, & Manahan‐Vaughan, ; Chen, Kolbeck, Barde, Bonhoeffer, & Kossel, ; Chen & Regehr, ).…”

“…Finally, through an examination of activity‐dependent plasticity, we found that LR hippocampus exhibits impaired LTP but normal LTD relative to HR. Due to known HR/LR differences in stress reactivity (Clinton et al, ; Kerman et al, ) and the effects of stress on LTP at CA3–CA1 synapses (Miller et al, ; Shors & Thompson, ), it is possible that HR/LR differences in LTP are related to these factors.…”

Feasibility of a Functional Medicine Approach to Slowing Clinical Cognitive Decline in Patients over Age 55: A Multiple Case Study Report

“…Physical activity as a neuroprotective practice has been well documented in the past decade [25][26][27][28], and with recent advances in medical technology we are now able to understand some of the underlying mechanisms of why this is so. Both human and animal trials establish the link between physical exercise and neurobiological improvements, such as brain plasticity, hippocampal stability, gray and white matter volume, neuronal fiber integrity, reduced inflammation, and increased brain-derived neurotropic factor (BDNF) levels [29][30][31][32][33][34][35]. However, there is a gap in the literature regarding the relationship between exercise, cognition, and brain network connectivity, which the current study attempts to address.…”

The Effects of Exercise on Long-Term Potentiation: A Candidate Mechanism of the Exercise-Memory Relationship

“…For example, from various determinants, such as epilepsy or sleep deprivation, exercise has been shown to revert the reduced CA1 (Cornu Ammonis-1) LTP [54,55]. Similarly, when exercise and stress occurs concurrently, exercise is able to combat the stress so that the dorsal hippocampus can experience normal levels of LTP [40]. Additionally, in Alzheimer's disease (AD) models, Aβ impairs CREB phosphorylation, and this impairment is prevented by regular exercise, which also relieves the ADinduced suppression of BDNF [35].…”