Physical exercise/melatonin interaction in young rats fed a low-protein diet: a behavioral, electrophysiological, and redox balance analysis

Introduction Early-life protein malnutrition disrupts redox balance in the brain and alters brain development and function. This study evaluated the effects of subcutaneous melatonin (MLT) administration, treadmill exercise (TE), and their combination on behavioral parameters (anxiety and memory), brain electrical activity (cortical spreading depression, CSD), and brain oxidative stress in well-nourished ( n = 40) and malnourished ( n = 40) young male rats. Methods Both well-nourished and malnourished rats were assigned to treadmill exercise ( n = 20) or sedentary ( n = 20) groups. Each group (exercised and sedentary) received either MLT (subcutaneous; n = 10/group) or vehicle ( n = 10/group). MLT (10 mg/kg on alternate days) and TE (forced running on a treadmill for 40-min daily sessions, 3 days/week) were conducted from P25 to P55. Immediately after TE and MLT treatments, animals underwent behavioral tests for anxiety (elevated plus maze and open field) and object recognition memory. CSD was continuously recorded for 4 h. Brains were collected for redox balance analyses. Results Malnutrition increased anxiety-like behaviors, impaired memory, accelerated CSD propagation, and disrupted cortical redox balance. Both MLT administration and TE reduced these adverse effects, improving behavioral performance, slowing CSD, and attenuating prooxidant markers. The combined interventions produced values closer to those of well-nourished animals. Conclusion The data suggest that melatonin and aerobic exercise have complementary neuroprotective effects in malnourished young rats, mitigating behavioral and electrophysiological disturbances and restoring brain oxidative balance. These interventions may be promising strategies for minimizing the consequences of early-life protein malnutrition on neurodevelopment.