Unraveling nanocurcumin role in the pathogenesis of chronic stress-induced neuronal damage in the frontal cortex and hippocampus of rats

Prolonged stress has been identified as a primary contributor to neurodegenerative conditions, affecting key regions of the brain like the hippocampus and frontal cortex. Curcumin, a natural substance with numerous biological properties such as antioxidant, antibacterial, and anti-inflammatory effects, has limited application due to its hydrophobic nature. By studying male Wistar rats, this research explored how nanocurcumin impacts neuronal damage caused by chronic stress in the frontal cortex and hippocampus. This study involved 24 adult male rats, which were categorized into three groups: control, stress (four hours of daily restraint stress for two weeks), and stress + nanocurcumin (received 100 mg/kg nanocurcumin before stress). After the treatment period, cognitive impairment was assessed using the Barnes maze. Subsequently, the animals were sacrificed, and biochemical and histological evaluations were performed. The Barnes maze parameters were enhanced in the stress + nanocurcumin group relative to the stress animals. In the stress + nanocurcumin group, blood levels of catalase (CAT), glutathione (GSH), and total antioxidant capacity (TAC) diminished, although serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) escalated in comparison to the stress group. Administration of nanocurcumin resulted in reduced GSH levels and elevated MDA levels in the brain. Moreover, in the stressed group administered nanocurcumin, the density of neuronal spines in the dentate gyrus (DG), CA1 and CA3 areas of the hippocampus exhibited an increase relative to the stress group. Nanocurcumin dramatically diminished stress-induced neuronal damage in the CA1, CA3, DG of the hippocampus, and prefrontal cortex. Based on these results, the administration of nanocurcumin exerts neuroprotective effects against chronic stress-induced neurodegeneration by targeting oxidative stress and improving memory impairment. Therefore, nanocurcumin can be considered a potential complementary option for preventing neurodegenerative disorders induced by chronic stress and associated memory impairment.