Occlusal disharmony promotes anxiety-like behaviours by suppressing Sirt1.

ABSTRACT

BACKGROUND: Previous studies have indicated that occlusal disharmony (OD) can promote anxiety-like behaviours. However, the specific molecules involved in the development of anxiety-like behaviours and their underlying mechanisms remain unknown. METHODS: OD was produced by anterior crossbite of female mice. We measured the anxiety levels of mice in each group and screened the hippocampal mRNA expression profiles of mice in the control group and OD group. The role of target mRNA in OD-induced anxiety-like behaviours was evaluated and we preliminarily explored the possible downstream pathways. RESULTS: The results suggested that OD can induce and promote anxiety-like behaviours with/without chronic unpredictable mild stress. We found that Sirt1 was significantly downregulated within the hippocampus in OD mice. In addition, the downregulation of Sirt1 within the hippocampus in OD and control mice promoted anxiety-like behaviours, increased acetylated histone H3 expression and decreased Dnah12 transcription levels. In contrast, in OD mice subjected to an injection of resveratrol, there was a remission of anxiety-like behaviours and an upregulation of Sirt1 in the hippocampus, the effects of which were accompanied by decreased acetylated histone H3 expression and increased Dnah12 transcription levels. CONCLUSIONS: OD leads to increased sensitivity to chronic stress in mice, resulting in anxiety-like behaviours. During this process, Sirt1 acts as an effective factor in the regulation of OD-induced anxiety-like behaviours. CLINICAL RELEVANCE OD, as a stressor, could induce anxiety-like behaviours. It investigates the impact of OD (a stressor) on the molecular genetic of the pathophysiology of major neuropsychiatric disorders.