メタボリックシンドロームジャーナル

The Brain Adenylyl Cyclase Signaling System and Cognitive Functions in Rats with Neonatal Diabetes under the Influence of Intranasal Serotonin

Abstract

Alexander O Shpakov, Kira V Derkach, Oksana V Chistyakova, Ivan B Sukhov, Valery N Shipilov and Vera M Bondareva

Type 2 diabetes mellitus is often associated with the neurodegenerative changes, and this is regarded as being the cause of cognitive deficit and other brain dysfunctions. The data obtained by us and the other authors showed that alterations in the brain signaling systems regulated by different hormones and neurotransmitters contribute to triggering and development of neurodegenerative processes in diabetes. However, the activity of brain adenylyl cyclase system and the cognitive functions, their interrelation, and the influence of intranasal serotonin on them in type 2 diabetes are poorly understood yet. We investigated the hormonal sensitivity of adenylyl cyclase system in the brain of female rats with the neonatal model of type 2 diabetes and the influence of 8-weeks treatment with intranasal serotonin (20 μ g/rat daily) on the brain adenylyl cyclase system and cognition in diabetes. It was shown that in the diabetic brain the regulatory effects of hormones (relaxin, adrenergic agonists, dopamine, serotonin) activating adenylyl cyclase via Gs proteins changed in a receptor-specific manner and were restored by intranasal serotonin. The effects of hormones inhibiting adenylyl cyclase via Gi proteins were significantly decreased, especially in the case of agonists of type 1 serotonin receptors. The intranasal serotonin treatment led to their partial or complete restoration. Using Morris water maze test we showed that intranasal serotonin improves diabetes- associated impaired learning and spatial memory. Summing up, in the brain of diabetic rats the functional activity of hormone-sensitive adenylyl cyclase signaling system was altered, most dramatically in the G i -coupled cascades. The intranasal serotonin treatment improved both the signal transduction via the brain adenylyl cyclase system and cognitive functions in type 2 diabetes.