NEUROPROTECTIVE ROLE OF RESISTANCE TRAINING IN POSTTRAUMATIC STRESS DISORDER ASSOCIATED WITH DIABETES

Abstract

Background: A substantial amount of evidence shows that people with posttraumatic stress disorder (PTSD) have a 2 to 3 times higher rate of premature mortality than the general population. Recently, this premature mortality has been pinpointed to the underlying role of cardio-metabolic diseases. Likewise, the prevalence of type two diabetes (T2DM) among this population has been determined, with studies demonstrating PTSD increasing the susceptibility of developing T2DM. The increased risk of cardio-metabolic diseases seen in patients with PTSD is partially accounted for by the intricate interplay of risk factors such as genetic factors, common pathophysiological mechanisms, and cardio-metabolic side effects resulting from the use of off-label psychotropic medications in patients with PTSD.

There is a growing amount of interest in the importance of physical fitness, specifically in cardiorespiratory fitness, as an essential modifiable risk factor for cardio-metabolic complications. However, resistance training (RT) and its significance in treating some diseases, including T2DM, have also been raised by many researchers as they have been shown to improve both neuromuscular and metabolic functions as well as body composition. Thus, our study aims to tackle both aspects by proposing a resistance exercise protocol performed at the aerobic threshold-glucose threshold. We consider that the glucose threshold (GT) could be another intriguing way to guide the workload in resistance training to obtain similar physiological effects to cardiorespiratory endurance exercise in addition to the benefits of strength training.

Aim: This study aims to confirm the feasibility of identifying the blood glucose threshold (GT) during resistance exercise by employing ladder-climbing, specifically in mice with diabetes with or without PTSD. Moreover, no study has investigated the long-term effects of resistance training at the glucose/aerobic threshold. Thus, this study also aims to discover neurological improvements, if any, in functions of mice with diabetes and PTSD.

Methods: Male C57BL/6J mice were used to conduct this study. Social defeat was used for the induction of PTSD in mice. Consequently, T2DM was induced using a combination of a high-fat diet and streptozotocin injections. Treatment groups underwent a resistance exercise program three times per week for five weeks. The cognitive function of the studied mice was assessed using the novel object recognition test. Hargreave’s and the electronic von Frey tests were used to evaluate sensory dysfunction verified by the presence of heat and mechanical hyperalgesia. To detect motor dysfunction raised beam walking test was conducted. Changes in body composition were also analyzed. Finally, at the molecular level, markers of ROS production were assessed in the prefrontal cortex and hippocampus.

Results: This study showed the possibility of identifying GT in diabetic mice through the implication of ladder-climbing resistance exercise. Exercise groups witnessed an improvement in body composition compared to diabetic and PTSD groups. Moreover, compared to the control group, PTSD and diabetic groups presented sensory, motor, and cognitive dysfunction based on behavioral and molecular tests. Exercise alleviated sensory and motor dysfunction, in addition to recognition memory loss. We suggest a plausible mechanism of the ameliorated condition to be through the observed subsequent decrease in NADPH-induced ROS production with resistance exercise.

Conclusion: Despite its invasive nature GT identification is a cost-efficient alternative in the absence of sophisticated equipment. Moreover, this study also sheds light on the potential neuroprotective role of resistance exercise.