Abstract
Malocclusion is an important risk factor for temporomandibular disorder (TMD), a series of disorders characterized by dysfunction in the orofacial region involving the temporomandibular joint (TMJ) and jaw muscles. We recently showed that experimental unilateral anterior crossbite (UAC) produced masseter hyperactivity through a circuit involving the periodontal proprioception, trigeminal mesencephalic nucleus (Vme), and trigeminal motor nucleus (Vmo). Anxiety is a common complication in patients with TMD. The lateral habenula (LHb) is involved in emotional modulation and has direct projections to the Vme. Therefore, the present research examined whether UAC facilitates excitatory input from the LHb to the Vme and, subsequently, anxiety-like behaviors in rats. The LHb activation was evaluated by the electrophysiological recording, assessment of vesicular glutamate transporter-2 (VGLUT2) mRNA expression, and measurement of anxiety-like behaviors. The effects of LHb activity on Vme were evaluated by electrophysiological recording from Vme neurons and local changes in VGLUT2 protein density. UAC produced anxiety in modeled rats and increased neuronal activity in the LHb. VGLUT2 mRNA expression was also increased in the LHb. Further, VGLUT2-positive boutons were observed in close apposite upon parvalbumin (PV)-labeled Vme neurons. VGLUT2 protein expression was also increased in the Vme. Significantly, injection of VGLUT2-targeted shRNA into the LHb reduced the expression of VGLUT2 protein in the Vme, attenuated UAC-associated anxiety-like behaviors, and attenuated electrophysiological changes in the Vme neurons. In conclusion, we show that UAC activates the LHb neurons as well as the periodontal proprioceptive pathway to provide excitatory input to the Vme and produce anxiety in rats. These findings provide a rationale for suppressing activity of the LHb to attenuate both the physical and psychological effects of TMD.
Highlights
Masseter hyperactivity is often observed in temporomandibular disorder (TMD), which is a collective term for a heterogeneous array of psychosocial and physiological disorders that is more prevalent in females (Klasser et al, 2018)
The elevated plus-maze test results showed that unilateral anterior crossbite (UAC) rats had a lower percentage of entries into open arms (OAs) (p < 0.05 at 2 weeks; p < 0.01 at 4, 8, and 12 weeks; Figure 1E) and a lower percentage of time spent in the OAs (p < 0.05 at 2 weeks; p < 0.01 at 4, 8, and 12 weeks; Figure 1F) than control rats did at 2 weeks after surgery
There is no direct evidence that increased vesicular glutamate transporter-2 (VGLUT2) protein in the Vme implies an increase in VGLUT2 expression in lateral habenula (LHb) neurons that project to the Vme, repression of VGLUT2 protein levels in the Vme by VGLUT2 mRNA expression in the LHb confirmed that mRNA and protein changes occurred among the same group of neurons
Summary
Masseter hyperactivity is often observed in temporomandibular disorder (TMD), which is a collective term for a heterogeneous array of psychosocial and physiological disorders that is more prevalent in females (Klasser et al, 2018) Based on both cross-sectional studies (Wang et al, 2009) and animal experiments (Huang et al, 2002; Henderson et al, 2015; Zhang et al, 2016), aberrant dental occlusion plays an adverse role in TMD. Occlusion determines muscular performance via periodontal–muscular feedback mechanisms that are modified by contact-mediated loading (Wang and Mehta, 2013) Contact changes, such as a posterior crossbite, are found in 8%–22% of humans (Agostino et al, 2014) and have an impact on chewing movements (Piancino et al, 2006, 2012). The UAC model could be used in explorations of Vme-related problems, which are worthy of investigation
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