Occlusal disharmony attenuates inhibitory synaptic transmission in the medial prefrontal cortex and contributes to anxiety.

Abstract

Background: It has been well-validated that Occlusal Disharmony (OD) induces negative emotions, especially anxiety. While it leads to considerable frustration for both doctors and patients, its underlying mechanisms remain unclear, and effective treatment has been lacking. The present study aims to explore the pathological mechanisms of OD induced anxiety and to find a straightforward yet effective treatment strategy for this ostensibly intricate clinical phenomenon.

Material and methods: OD mice were established through binding a metal tube to their right mandibular incisor. Then, the mental state of the mice was assessed by various behavioral experiments. Additionally, the mood of OD mice was also evaluated similarly before and after the injection of mifepristone. Furthermore, neuronal excitability in the mPFC was examined by immunofluorescence and electrophysiology, with the potential mechanisms investigated through Western blotting.

Results: OD mice exhibited anxiety-like behavior, and the administration of mifepristone, an anxiolytic drug, could alleviate it. Subsequently, an increase in n[1]euronal excitability was observed, accompanied by a reduction in the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in the medial prefrontal cortex (mPFC). In addition, the expression of erb-b2 receptor tyrosine kinase 4 (ERBB4) and neuregulin 1 (NRG1), proteins associated with inhibitory neurotransmitter release, were found to be significantly downregulated in the mPFC.

Conclusion: OD attenuates GABAergic synaptic transmission in the mPFC, which may be the neural mechanism of anxiety caused by OD. But this phenomenon could be effectively alleviated by anti-anxiety treatment.