Therapeutic Effect of Exercise on Anxiety and Bowel Oxidative Stress in the Maternal Separation Animal Model

Abstract

According to evidence, Early-Life Stress (ELS), mood disorders, and medical comorbidities, i.e. Irritable Bowel Syndrome (IBS), are correlated; however, the direct contribution of ELS to IBS manifestations is less understood. The current study aimed at evaluating the effect of voluntary exercise on the mitochondrial dysfunction of the bowel fibroblasts, following the confirmation of anxiety behavior. Methods: In this study, Postnatal Day (PND) rats underwent Maternal Separation (MS), as a valid animal model of the brain-gut axis dysfunction, in the days 2-14; three hours daily. On day 21, the study animals were divided into 4 groups, as follows: control, Running Wheel (RW) exercise, MS, and MS+RW groups. The study groups were housed in separate cages (4 rats per cage) until the onset of intervention. On day 60, the elevated plus-maze was used to assess anxiety-like behaviors; the level of oxidative stress biomarkers, i.e. Reactive Oxygen Species (ROS), Glutathione (GSH) , as well as Adenosine Triphosphate (ATP) was measured to determine the gut mitochondrial function. Results: Findings revealed that ELS affected the gut energy metabolism in the studied rats; the negative effects of MS on anxiety and the gut mitochondrial dysfunction decreased via RW exercise during adolescence. Conclusion: Overall, anxiety behaviors and ROS production, leading to increased GSH and ATP levels, improved after RW exercise; this significantly impacts the function of colon secretory mitochondria. According to the positive effects of RW exercise on mitochondrial dysfunction in an ELS animal model, a potential relationship was found between the brain and gut in the study rats.

The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome

“…In line with data reported by other authors [ 10 , 20 ], our findings indicate dysfunctional mitochondrial biogenesis [ 35 ] in IBS-Std rats, which appeared to be associated with increased oxidative stress and inflammation in the gut.…”

“…This study aimed to evaluate the KD efficacy in reducing the harmful effects of stress on gut mitochondrial biogenesis using an animal model mimicking the brain–gut axis alterations. The obtained findings support the possible involvement of gut mitochondrial abnormalities in the functional comorbidities associated with IBS [ 10 , 20 ].…”

“…Limited research has explored the effects of chronic psychosocial stress [ 10 ] or early-life stress (ELS) on gut mitochondria [ 20 ], leading to the conclusion that mitochondrial activity was disturbed [ 10 , 20 ]. On these bases, the present study aimed to evaluate the KD efficacy in reducing the harmful effects of stress on gut mitochondrial functions.…”

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis

“…The complexity of these interactions between the brain and gut is presumably through "gut-brain axis" ( [85]. By realizing the importance of microbiome in modulating health, the gut-brain axis has been renamed as the GMB axis, which represents a complex network of communication between the gut, intestinal microbiome, and brain that seem to modulate immune system, gastro-intestinal tract, behavior, stress response, and CNS functions [15][16][17][85][86][87][88][89][90][91][92][93][94] (Fig. 2).…”

Early Adversity and Accelerated Brain Aging: A Mini-Review

“…MS evokes dysregulation of mitochondrial sirtuins within the PFC that persist well into middle-aged life (15 months) ( Pusalkar et al, 2016 ), and robust decreases in mitochondrial mass in the periphery, namely the muscle, noted 8 months post the cessation of MS ( Ghosh et al, 2016 ). Further, MS animals exhibit enhanced sensitivity to oxidative stress in peripheral mononuclear cells, noted until 18 months of age, and also reported in gut epithelial cells when examined in adulthood (2 months) in MS animals ( Grigoruta et al, 2020 ; Khorjahani et al, 2020 ). Impaired calcium homeostasis, enhanced ROS and a decrease in oxygen consumption rate (OCR) or ATP production is also reported in the PFC, raphe and hippocampus of adult (2–6 month) MS animals, suggestive of a broad mitochondrial dysfunction in multiple systems ( Della et al, 2013 ; Amini-Khoei et al, 2017 ; Masrour et al, 2018 ; Nold et al, 2019 ).…”