Neuroendocrine Mechanism of Anxiety-/Depression-like Behaviors by the Bilateral Neurectomy of Hypoglossal Nerves in Rats

Abstract

It has been reported that oral sensory and motor stimulations are necessary to maintain normal function of the hippocampus. In rodent models, disrupted oral sensory relay to brain increased depression-like behaviors with a hippocampal dysfunction, and oral motor dysfunctions impaired hippocampus-dependent cognitive function. Hippocampus exerts negative feedback regulation on the hypothalamic-pituitary-adrenal (HPA) axis, and the HPA axis dysfunction has been implicated in psycho-emotional disorders. Hypoglossal nerve controls tongue movements and damages of it result in difficulty in mastication and deglutition. This study was conducted to examine if tongue motor loss with bilateral neurectomy of hypoglossal nerves (HN) induces psycho-emotional adversities in relation with an HPA axis dysfunction. Male SD rats were subjected to elevated plus maze (EPM) or forced swim tests at two weeks after the HN or sham surgery. The hypothalamic phosphorylated extracellular signal-regulated kinase (pERK) and the pituitary pro-opiomelanocortin (POMC) expressions were examined by western blot analysis and the plasma corticosterone by ELISA. Open arm stay was decreased, but closed arm stay was increased, in HN rats during EPM test. Immobility duration of HN rats during swim test was increased and struggling decreased. Increases in the plasma corticosterone levels and adrenal hypertrophy were observed in HN rats. The hypothalamic pERK and the pituitary POMC expressions were decreased in HN rats. Results suggest that bilateral neurectomy of hypoglossal nerves increases anxiety-/depression-like behaviors in rats, possibly in relation with the HPA axis dysfunction.