Evaluating the effect of intranasal insulin administration on spatial memory in an animal model of Alzheimer's disease; the role of mitochondrial biogenesis

Abstract

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disease, which is associated with progressive cognitive disorders and memory loss. Insulin has recently gained more attention for its anti-inflammatory, cognitive, and protective effects. This study aimed to investigate the effect of intranasal insulin administration on cognitive functions and mitochondrial biogenesis in rats treated with streptozotocin (STZ). Materials and Methods: In this experimental study, 32 adult male Wistar rats were used. Correspondingly, to induce an animal model of AD, STZ was injected bilaterally in the lateral ventricles (3 mg/rat; 3 μl/ventricle). Morris water maze was used to investigate cognitive disorders and confirm the induction of the AD animal model. Treatment was performed by intranasal insulin administration (2 IU/rat/day; 10 μl/nostril) after STZ injection for 14 consecutive days. Changes in the expression of genes involved in mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM) were measured by Real-time PCR technique in the hippocampus. Results: The results of the study showed that STZ injection led to spatial memory disorder concomitant with a decrease in the expression of genes involved in mitochondrial biogenesis in the hippocampus of rats. Whereas, intranasal insulin administration reduced cognitive disorders and increased the expression of genes involved in mitochondrial biogenesis in the hippocampus of animals treated with STZ. Conclusion: Insulin can reduce STZ-induced cognitive disorders by affecting the mitochondrial biogenesis pathway, so it can be considered an important target for reducing cognitive deficits in AD patients.