Resumen:
Type 1 diabetes mellitus (T1DM) and postmenopausal estrogen depletion represent risk factors for neurobiological imbalances, promoting a neurodegenerative environment in the hippocampus characterized by oxidative stress, neuroinflammation, and programmed cell death. Although strategies such as physical training and supplementation with the polyphenol curcumin have independently demonstrated neuroprotective potential, the synergistic effects of these interventions in the coexistence of both conditions remain unexplored. Therefore, the present study aimed to investigate the effects of moderate-intensity aerobic physical training and curcumin administration, both individually and in combination, on histopathological, oxidative, inflammatory, and apoptotic parameters in the hippocampus of ovariectomized (OVX) rats with T1DM. Twenty-four rats underwent ovariectomy, and T1DM was induced by streptozotocin (STZ, 40 mg/kg) administration. Subsequently, the animals were divided into four groups: Sedentary Diabetic OVX (SDO), Sedentary Diabetic OVX treated with Curcumin (SDO+CUR), Trained Diabetic OVX (TDO), and Trained Diabetic OVX treated with Curcumin (TDO+CUR) (n=6 per group). The intervention protocol lasted eight weeks, five days per week, during which trained groups underwent treadmill running sessions, while supplemented groups received curcumin via gavage (100 mg/kg body weight), five days per week. At the end of the experimental period, hippocampal tissue was dissected for the evaluation of neuronal morphology and integrity, quantification of oxidative damage biomarkers, such as lipid peroxidation products and nitrites, and measurement of endogenous antioxidant enzyme activity. Additionally, key markers of inflammatory pathways, MAP kinase signaling, and apoptotic profiles were analyzed using immunohistochemistry, immunofluorescence, gene expression, and ELISA techniques. The results demonstrated that the combination of physical training and curcumin reduced pyknosis, oxidative damage markers, Bax/Bcl-2 ratio, and caspase-3 expression. Moreover, the combined therapy enhanced the activity of the antioxidant enzymes SOD and GPx, as well as BDNF gene expression. The isolated interventions also modulated specific parameters: physical training improved neuronal morphology and SIRT1 expression, while curcumin increased cell density and reduced NF-κB, TNF-α, and GFAP expression in hippocampal tissue. In conclusion, these findings indicate that the association between aerobic physical training and curcumin promotes a synergistic neuroprotective response, evidenced by the attenuation of multiple markers of cellular damage in the hippocampus. This finding suggests that the combination of these therapeutic strategies may be more effective than isolated interventions in mitigating neurodegenerative processes in an experimental model of T1DM and postmenopause.
