The effects of vagal nerve stimulation and high fructose consumption on neuropsychiatric symptoms associated with alzheimer's disease model in rats

Neuropsychiatric symptoms (NPS) were seen in almost all patients diagnosed with Alzheimer's disease (AD) however there is no efficient drug therapy yet. In recent years, vagal nerve stimulation (VNS) has been used for treatment of epilepsy, depression and migraine, might be an alternative therapy for NPS in AD. High fructose consumption (HFCS) was shown to be a significant factor in the etiology of AD but there is no data about its' effects on NPS observed in AD. We aimed to investigate the effects of VNS and fructose consumption on NPS in an rat model of AD. AD model achieved by injecting Aβ in the lateral ventricles. In the AD model, rats showed depression, decreased aggressive behavior and memory disorders similar to that of NPS in AD. AD groups of rats when treated with high fructose corn syrup for 3 weeks, they displayed an increase in aggression and a decrease in depression-like behaviors respect to the rats with AD. In rats treated with VNS for 14 days, behavioral alterations such as reduced weight gain, antidepressant, anxiolytic, lower aggression scores, increased locomotor activity, and increased memory performance were observed. In the hippocampus, NMDAR2B level decreased by 31% in the control group after VNS, while NMDAR2A level increased by 91%. Increased locomotor activity after VNS was correlated with NMDAR2B reduction. Although, all the behavioral effects of VNS are also seen in AD model rats, NMDAR2A levels did not increased after VSU administration. According to these results, VNS shows these behavioral effects in AD model rats via a mechanism independent of NMDAR2A levels. In this thesis we have found that consumption of HFCS increased the NPS observed in the AD rat model. VNS improved cognitive functions and caused positive behavioral alterations which makes VNS a effective candidate for the treatment of NPS seen in AD.