EFFECTS OF INTRANASAL INSULIN ON CENTRAL NERVOUS SYSTEM REDOX HOMEOSTASIS

Alzheimer’s disease is characterized by brain insulin resistance and metabolic dysfunction. Consequently, intranasal insulin is recognized as a promising therapy due to its ability to directly access the central nervous system, bypassing the blood-brain barrier. However, the region-specific impact of acute insulin administration on central redox homeostasis remains unclear, particularly regarding regional heterogeneity. Male Wistar rats were treated with a single intranasal dose of 2 IU insulin and sacrificed at 3, 7.5, 15, 30, 60, and 120 minutes after administration. Lipid peroxidation (TBARS), total reductive capacity (ABTS), thiol concentrations (LMWT, SH), and superoxide dismutase (SOD) activity were measured in plasma, respiratory and olfactory epithelia, and seven brain regions. The results were correlated with insulin signaling parameters from the same samples. Results revealed rapid, region-specific changes in redox markers. Nasal epithelia showed increased reductive capacity and a positive correlation between AMPK activation and thiol levels. However, metabolically sensitive regions, such as the hippocampus and hypothalamus, showed a temporary decrease in antioxidant capacity and thiol levels. The temporal cortex demonstrated the strongest link between insulin signaling and redox status, while cortical regions generally displayed specific alterations in lipid peroxidation. Intranasally administered insulin acts as a strong modulator of CNS redox homeostasis with specific regional effects. In peripheral epithelia, it activates a rapid antioxidative defense, while deeper brain structures may experience temporary oxidative stress. These results demonstrate the complex, region-specific nature of central insulin action, suggesting that dosage must be carefully optimized.