The effect of intra-nasal insulin & growth factor-rich serum administration on memory and behavior defects induced by icv-STZ rat model and correlation analysis of hippocampus oxidative-nitrosative state with spatial memory and anxiogenic behavior

Abstract

AbstractImpaired insulin and growth factor functions are thought to drive many of the alterations observed in neurodegenerative disease and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuroprotection in brain damage induction models for rodents. In the present study. Growth factor-rich serum (GFRS) is a serum separated from activated platelets used intranasally with the cotreatment of insulin to examine the effects of intranasal treatments on memory and behavioral defects induced by icv-STZ rat model and the correlation of hippocampus oxidative state with memory and behavior scores analyzed. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze (MWM), leads to anxiogenic-like behavior in the open field arena, and induces oxidative stress in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning and memory and induced anxiolysis. The present study showed that cotreatment (GFRS + insulin with respective dose) has stronger protection against hippocampus oxidative stress in comparison with a single therapy. Memory and behavioral improvements with insulin and GFRS could be attributed to the oxidative stress reduction in the hippocampus as shown by significant correlation between hippocampus oxidative-nitrosative stress and memory/behavior scores.