Aerobic and Resistance Exercise Modalities Ameliorate Hippocampal Plasticity and Neurocognitive Changes Induced by Receiving Nandrolone Decanoate in Rats (Physiological, Biochemical, and Histological Study)

Anabolic-androgenic steroids (AAS), such as ND, are commonly used to enhance physical performance and muscle mass. However, its abuse has been associated with numerous adverse health effects, particularly on the hippocampus, affecting learning, working memory, and cognitive functions. The current study aims to investigate the potential effects of ND, aerobic exercise, resistance exercise, and the combination of ND with aerobic or resistance exercise on memory and cognitive functions. Moreover, the study aims to explore the possible underlying mechanisms of changes in memory and cognitive function. Adult male rats were divided into four groups: control (GI), only ND-treated (GII), only exercise (GIIIa & GIIIb), and combined exercise + ND-treated (GIVa & GIVb). Exercise included aerobic treadmill training and ladder-climbing modalities for 8 weeks, either alone or with ND. Cognitive function was evaluated using the Modified Barnes Maze and T-maze tests. Hippocampal integrity was assessed through oxidative stress markers, hippocampal brain-derived neurotrophic factor (BDNF) levels, hippocampal nerve growth factor (NGF) expression, and histological examination. ND significantly impaired spatial learning and memory, increased oxidative stress, lowered hippocampal BDNF levels, and reduced NGF expression in the hippocampus. Exercise markedly attenuated these harmful effects. Aerobic exercise gave the most pronounced improvements. It restored cognitive function, enhanced antioxidant defenses, increased hippocampal BDNF levels, increased hippocampal NGF expression, and preserved hippocampal structure. Resistance training also had neuroprotective effects, but to a lesser extent than aerobic exercise. In brief, both aerobic and resistance exercise have been shown to exert protective effects against ND-induced neurotoxicity by enhancing antioxidant defenses and promoting neuronal integrity. The monitored neuroprotective benefits suggest that physical exercise could serve as a possible non-pharmacological approach to prevent or decrease cognitive impairments associated with anabolic steroid abuse.