心理压力通常被认为与咀嚼肌疾病密切相关,这是颞下颌关节紊乱病(TMD)的主要症状。先前的研究已经证实,暴露于压力下可能会导致咀嚼肌肉过度活跃。然而,这一过程的核心机制尚不清楚.中脑三叉神经核(VME),驻留在脑干中,是咀嚼本体感觉的主要传入中心,并通过投射到三叉神经运动核(Vmo)在口腔运动中发挥关键作用。因此,本研究旨在研究Vme神经元在慢性应激诱导的咬肌过度活动中的作用。我们发现,使小鼠经受约束应激(6小时/天)14天引起明显的焦虑样行为,明显的咬肌过度活动,显著增强Vme神经元的电生理兴奋性。通过使用顺行道示踪结合免疫荧光染色方法,我们观察到从Vme到Vmo的囊泡谷氨酸转运体1(VGLUT1)阳性的谷氨酸能投射。此外,慢性束缚应激(CRS)升高Vmo中VGLUT1和胆碱乙酰转移酶(ChAT)的表达。此外,将VGLUT1靶向的短发夹RNA(shRNA)施用到双侧Vme中显着抑制了Vme神经元的增强的过度兴奋性,下调VGLUT1和ChAT在Vmo中的过表达,并减轻CRS引起的咬肌过度活动的升高。一起来看,我们证明了CRS可以激发VME中的神经元,增强从Vme到Vmo的谷氨酸能兴奋性投射,并导致咬肌过度活动。这些发现为我们提供了一种新的心理因素与TMD之间相关性的中心机制。
Psychological stress is commonly accepted to be closely associated with masticatory muscle disorder, which is the main symptom of temporomandibular disorder (TMD). Previous studies have confirmed that exposure to stress may cause masticatory muscle hyperactivity. However, the central mechanism underlying this process remains unclear. The mesencephalic trigeminal nucleus (Vme), which resides in the brainstem, is the primary afferent center for masticatory proprioception and plays a key role in oral-motor movements by projecting to the trigeminal motor nucleus (Vmo). Therefore, the present study was designed to examine the role of Vme neurons in masseter overactivity induced by chronic stress. We found that subjecting mice to restraint stress (6 h/day) for 14 days caused significant anxiety-like behavior, obvious masseter overactivity, and markedly enhanced electrophysiological excitability of Vme neurons. By using anterograde tract tracing combined with immunofluorescence staining methods, we observed vesicular glutamate transporter 1 (VGLUT1)-positive glutamatergic projections from the Vme to the Vmo. Moreover, chronic restraint stress (CRS) elevated the expression of VGLUT1 and choline acetyltransferase (ChAT) in Vmo. Furthermore, administration of VGLUT1-targeted short hairpin RNA (shRNA) into the bilateral Vme significantly suppressed the enhanced overexcitability of Vme neurons, downregulated the overexpression of VGLUT1 and ChAT in the Vmo, and attenuated the elevated overactivity of the masseter caused by CRS. Taken together, we showed that CRS can excite neurons in the Vme, enhancing glutamatergic excitatory projections from the Vme to the Vmo and resulting in masseter muscle overactivity. These findings provide us with a novel central mechanism underlying the correlation between psychological factors and TMD.