Vagus Nerve Stimulation Exerts the Neuroprotective Effects in Obese-Insulin Resistant Rats, Leading to the Improvement of Cognitive Function

Abstract

Vagus nerve stimulation (VNS) therapy was shown to improve peripheral insulin sensitivity. However, the effects of chronic VNS therapy on brain insulin sensitivity, dendritic spine density, brain mitochondrial function, apoptosis and cognition in obese-insulin resistant subjects have never been investigated. Male Wistar rats (n = 24) were fed with either a normal diet (n = 8) or a HFD (n = 16) for 12 weeks. At week 13, HFD-fed rats were divided into 2 groups (n = 8/group). Each group was received either sham therapy or VNS therapy for an additional 12 weeks. At the end of treatment, cognitive function, metabolic parameters, brain insulin sensitivity, brain mitochondrial function, brain apoptosis, and dendritic spines were determined in each rat. The HFD-fed with Sham therapy developed brain insulin resistance, brain oxidative stress, brain inflammation, and brain apoptosis, resulting in the cognitive decline. The VNS group showed an improvement in peripheral and brain insulin sensitivity. VNS treatment attenuated brain mitochondrial dysfunction and cell apoptosis. In addition, VNS therapy increased dendritic spine density and improved cognitive function. These findings suggest that VNS attenuates cognitive decline in obese-insulin resistant rats by attenuating brain mitochondrial dysfunction, improving brain insulin sensitivity, decreasing cell apoptosis, and increasing dendritic spine density.

Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial Dysfunction, and Dementia

“…Obese-insulin resistance caused by HFD consumption not only induced systemic inflammation, but also caused brain inflammation, as shown by increased brain pro-inflammatory cytokine; TNF-α and a transcriptional factor; NF-κB ( 13 , 15 , 19 , 116 ). Furthermore, brain oxidative stress was shown by an elevation in cytotoxic aldehyde products; MDA was also found in association with the brain inflammation following obese-insulin resistance ( 8 , 11 , 13 – 15 , 19 , 28 – 31 ).…”

“…Previous studies reported that mitochondrial dysfunction has been related to the development of insulin resistance ( 26 , 27 ). Interestingly, it has been shown that brain mitochondrial dysfunction, as indicated by the overproduction of mitochondrial reactive oxygen species (ROS), mitochondrial depolarization and mitochondrial swelling, has occurred in association with brain insulin resistance and all of these events could lead to the development of cognitive decline and Alzheimer's disease ( 6 , 8 , 11 , 13 – 15 , 19 , 28 – 31 ).…”

Improving Effects of Hop-Derived Bitter Acids in Beer on Cognitive Functions: A New Strategy for Vagus Nerve Stimulation

“…Several studies have reported that vagus nerve stimulation has beneficial effects on cognitive functions [71][72][73]. However, established procedures to stimulate the vagus nerve require surgery to implant electrophysiological devices, implicating safety and complication risks.…”

Mechanisms of Neuroprotective Effects of Peptides Derived from Natural Materials and Their Production and Assessment

“…Neuroprotection is mainly determined using behavioral activity tests of an animal model as well as biochemical assays (for example, of inflammatory cytokines and oxidative stress factors) using the tissues of animal models. Animal models have greatly advanced the understanding of AD pathogenesis (Phillips, Michell, Pruess, & Barker, ), and many animal studies have examined neuroprotective peptides (Chunchai et al., ; Nagahara et al., ; Wang et al., ). Behavioral studies in animal models of neurodegenerative disease have mainly been conducted using the Morris water maze test, probe trial, passive avoidance test, and locomotor activity tests.…”