Physical activity as a promoter of stress resilience: An analysis of behavioral effects and brain connectivity with cytochrome c-oxidase activity in adult male Wistar rats.

Physical activity (PA) is very beneficial for physical and mental health. This study aims to examine the resilience-inducting effect of PA in adult male Wistar rats exposed to unpredictable chronic mild stress (UCMS). Furthermore, we analyzed the influence of PA on behavioral tasks and functional brain connectivity with cytochrome c oxidase technique. The cytochrome c oxidase (CCO) is a mitochondrial enzyme involved in oxidative phosphorylation and ATP generation. For this analysis, we included five groups: Basal (n = 10, to determine the basal level of brain activity), Behav (n = 15, subjected exclusively to behavioral tests), PA (n = 10, exposed to physical activity), UCMS (n = 15, subjected to a stress protocol) and PA + UCMS (n = 15, exposed to PA prior to stress). The UCMS protocol consisted of randomly presenting several different stressors over four consecutive weeks. We evaluated several behaviors of the Behav, UCMS, and PA + UCMS groups. This assessment includes the hedonic responses using the sucrose consumption task, unconditioned anxiety with the zero maze, and coping strategies assessed with the cat odor test. The UCMS group showed an anhedonia profile and increased anxiety compared with the other groups. Although in the exposure to cat odor test, the PA + UCMS remained for the same time in the cat odor compartment as the other groups, it did not approach the odor, showing that it detected the risk. This response is more adaptive than the responses of the UCMS and Behav groups. An exploratory analysis of the cerebral connections showed an increase in CCO activity in the UCMS group compared to the other groups. This overactivity was reduced in dorsal Cornu Ammonis 3(dCA3) by prior PA. In this region, PA + UCMS showed similar activity as the groups not subjected to chronic stress. Therefore, PA can prevent the harmful effects of chronic stress on dCA3.

Impact of environmental enrichment on the GABAergic neurons and glucocorticoid receptors in the hippocampus and nucleus accumbens of Wistar rats: Pro-resilient effects.

The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models. Our work aims to evaluate the impact of environmental enrichment on male Wistar rats in an animal model for depression. For this purpose, we aim to assess changes in GR and GABAergic (PV+) density in cerebral regions related to cognitive-affective processes associated with depressive disorder, such as the dorsal- ventral hippocampus and accumbens nuclei. Three groups of rats were used: UCMs (unpredictable chronic mild stress), EE+ UCMs (enrichment + stress) and CONT (behavioral tests only). Hedonic responses elicited by sucrose solution were examined by licking behavior analysis; the anxiety level was evaluated using the elevated zero maze and the forced swimming (passive coping) tests. The environmental enrichment reduced the effects of chronic stress, promoting greater resilience. Thus, the UCMs group showed an anhedonia response, more anxiety and immobility behavior than either the control or the EE+ UCMs groups. Regarding immunochemistry results, there was a reduction in GABAergic activity coupled with increased activation of GR in UCMs in the dorsal hippocampus, but there were no differences between groups in the ventral hippocampus. These results suggest environmental enrichment could enhance greater resilience, reducing the vulnerability of the subjects to develop disorders such as depression and anxiety.

Reorganization of Brain Networks as a Substrate of Resilience: An Analysis of Cytochrome c Oxidase Activity in Rats.

The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models, showing adequate predictive validity. Our work aims to evaluate the effects of environmental enrichment (EE) on resilience in this experimental model of depression. We also aim to assess changes in brain connectivity using cytochrome c oxidase histochemistry in cerebral regions related to cognitive-affective processes associated with depressive disorder: dorsal hippocampus, prefrontal cortex, amygdala, accumbens, and habenula nuclei. Five groups of rats were used: UCMS, EE, EE + UCMS (enrichment + stress), BG (basal level of brain activity), and CONT (behavioral tests only). We assessed the hedonic responses elicited by sucrose solution using a consumption test; the anxiety level was evaluated using the elevated zero maze test, and the unconditioned fear responses were assessed by the cat odor test. The behavioral results showed that the UCMS protocol induces elevated anhedonia and anxiety. But these responses are attenuated previous exposure to EE. Regarding brain activity, the UCMS group showed greater activity in the habenula compared to the EE + UCMS group. EE induced a functional reorganization of brain activity. The EE + UCMS and UCMS groups showed different patterns of connections between brain regions. Our results showed that EE favors greater resilience and could reduce vulnerability to disorders such as depression and anxiety, modifying metabolic brain activity.