Effects of chronic vagal nerve stimulation in the treatment of β-amyloid-induced neuropsychiatric symptoms

Alzheimer's Disease (AD) is the leading cause of dementia and, at the time of diagnosis, half of AD patients display at least one neuropsychiatric symptom (NPS). However, there is no effective therapy for NPSs; furthermore, current treatments of NPSs accelerate cognitive decline. Due to the ineffectiveness and negative consequences of current treatments for NPSs, new approaches are strongly needed. Currently, indications for vagal nerve stimulation (VNS) include epilepsy, stroke rehabilitation and major depression but not NPSs or AD. Therefore, we investigated whether chronic VNS can treat NPSs in a rat model of AD. Here, we report the intracerebroventricular injection of amyloid-β (Aβ) results in depression-like behaviors and memory impairment in rats. Chronic VNS (0.8 mA, 500 μs, 30 Hz, 5 min/day) showed strong antidepressant and anxiolytic effects, and improved memory performance. Additionally, the anxiolytic effect of VNS was retained in the non-Aβ-treated rats. VNS also decreased aggressiveness and increased locomotor activity in both Aβ-treated and non-Aβ-treated rats. Recent studies showed VNS alters glutamatergic receptor levels, thus levels of GluA1, GluN2A, and GluN2B were determined. A significant reduction in GluN2B levels was seen in the hippocampus of VNS-treated groups which may relate to the anxiolytic effects and increased locomotor activity of VNS. In conclusion, VNS could be an effective treatment of NPSs, especially depression and anxiety, in AD patients without impairing cognition.