Intranasal Insulin Enhances Intracerebroventricular Streptozotocin-Induced Decrease in Olfactory Discriminative Learning via Upregulation of Subventricular Zone-Olfactory Bulb Neurogenesis in the Rat Model.

Abstract

Olfactory perception and learning play a vital role in the animal's entire life for habituation and survival. Insulin and insulin receptor signaling is well known to modulate the olfactory function and is also involved in the regulation of neurogenesis. A very high density of insulin receptors is present in the olfactory bulb (OB), the brain area involved in the olfactory function, where active adult neurogenesis also takes place. Hence, our study was aimed to explore the effect of intranasal insulin treatment and the involvement of the subventricular zone-olfactory bulb (SVZ-OB) neurogenesis on olfactory discriminative learning and memory in intracerebroventricular streptozotocin (ICV STZ) rat model. Our findings revealed that intranasal insulin treatment significantly increased ICV STZ-induced decrease in the olfactory discriminative learning. No significant change was observed in the post-treatment olfactory memory upon ICV STZ and intranasal insulin treatment. ICV STZ also caused a substantial decline in the SVZ-OB neurogenesis, as indicated by the reduction in the number of 5-bromo-2'-deoxyuridine (BrdU+) cells, BrdU+ Nestin+ cells, and Doublecortin (DCX+) cells, which was reversed by intranasal insulin treatment. Intranasal insulin treatment also increased the number of immature neurons reaching the olfactory bulb (OB) as indicated by an increase in the DCX expression in the OB as compared to the ICV STZ administered group. ICV STZ administration also resulted in the modulation of the expression of the genes regulating postnatal SVZ-OB neurogenesis like Mammalian achaete scute homolog 1 (Mash 1), Neurogenin 2 (Ngn 2), Neuronal differentiation 1 (Neuro D1), and T box brain protein 2 (Tbr 2). Intranasal insulin treatment reverted these changes in gene expression, which might be responsible for the observed increase in the SVZ-OB neurogenesis and hence the olfactory discriminative learning.