Impact of Transcutaneous Auricular Vagus Nerve Stimulation on Spatial Learning and Memory in Acrolein-Induced Alzheimer’s Disease-Like Hippocampal Neuronal Damage in Wistar Rats

Abstract

Background: Data about the utility of vagus nerve stimulation (VNS) as a potential therapy for neurodegenerative disorders are still inconclusive. We used a rat model of acrolein-induced hippocampal neurodegeneration to investigate the effect of VNS on spatial learning and memory. Methods: A total of 24 Wistar rats were randomly allocated to one of the four groups: no acrolein exposure (n = 6), control (n = 6), sham (n = 6), and experimental (n = 6). The control, sham, and experimental groups were exposed to acrolein 2.5 mg/kg/day by gastric gavage for eight weeks. After acrolein exposure, the experimental and sham groups received transcutaneous auricular VNS and greater auricular nerve stimulation, respectively, under 2% isoflurane anesthesia for four weeks. Then, all animal groups were assessed for spatial learning and memory in a Morris water maze before being euthanized for hippocampus histological examination. Results: The mean time to find the hidden platform varied significantly between the no acrolein exposure group and each of the acrolein-exposed groups. The results of one-way ANOVA indicated a significant difference in the average swimming time between the four study groups (F = 14.64, p < 0.001). Results from the post-hoc analysis indicated that the mean difference was statistically significant between the “no “experimental” groups (p = 0.001), and between the “control” and “sham” groups (p < 0.001). There was no statistically significant difference in swimming time to find the hidden escape platform between the sham and experimental groups (p = 0.060). Conclusion: Transcutaneous auricular VNS has no significant effect on spatial learning or memory in Wistar rats with acrolein-induced hippocampus neuronal damage, indicating the need to review the long-standing notion that hippocampal neuronal loss causes spatial navigation deficits.