Impact of Short-term Rehabilitation on Chronic Stress-induced Brain Alterations and Associated Cognitive Deficits.

Background: Persistent stress is frequently comorbid with major depressive disorder and anxiety, leading to significant psychological and behavioural impairments. However, the neurophysiological mechanisms underlying stress reversal remain poorly understood. Although several reversal strategies, including pharmacological antidepressants, brain stimulation therapies and nutritional interventions, have been explored, their outcomes remain inconsistent. Purpose: This study aimed to evaluate the effectiveness of rehabilitation as a non-pharmacological intervention for reversing stress-induced behavioural and neurobiological alterations. Methods: Chronic stress was induced in rats, followed by short-term rehabilitation through standard housing conditions without additional physical or behavioural enrichment. Behavioural assessments, including learning and memory tests, the open field test (OFT) and the elevated plus maze (EPM), were conducted to evaluate cognitive, exploratory and anxiety-like behaviours. Morphological changes in specific brain regions were examined and correlated with molecular markers, including neurotrophic factors and astrocytic markers. Results: Short-term sedentary rehabilitation failed to reverse stress-induced behavioural abnormalities and brain region alterations. Chronically stressed rats exhibited significant learning and memory deficits, reduced exploratory behaviour in the OFT, and altered anxiety-like behaviour in the EPM. These behavioural impairments were accompanied by morphological changes and dysregulation of neurotrophic and astrocytic markers, indicating insufficient neuroplastic recovery under sedentary rehabilitation conditions. Conclusion: The findings highlight the limited efficacy of short-term, non-enriched rehabilitation in reversing chronic stress-induced neurobehavioural alterations. The study underscores the importance of lifestyle-based therapeutic approaches, including behavioural, physical and relaxation therapies, for effective stress reversal. Interventions such as social support, exercise, enriched environments, and task-based learning-analogous to cognitive behavioural therapy-may offer greater neuroprotective and restorative benefits. These findings provide translational relevance for developing social rehabilitation strategies in clinical conditions associated with overwhelming stress and stress-related cognitive deficits.