Malocclusion Generates Anxiety-Like Behavior Through a Putative Lateral Habenula-Mesencephalic Trigeminal Nucleus Pathway
Malocclusion Generates Anxiety-Like Behavior Through a Putative Lateral Habenula-Mesencephalic Trigeminal Nucleus Pathway
复制标题
咬合不正通过假定的外侧缰核-中脑三叉核通路产生焦虑样行为
DOI：
10.3389/fnmol.2019.00174
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发表时间：
2019-07-30
影响因子：
4.8
通讯作者：
Wang, Mei-Qing
中科院分区：
文献类型：
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作者：
Liu, Xin;Zhou, Kai-Xiang;Wang, Mei-Qing
颞下颌关节紊乱（temporomandibular disorder， TMD）是一系列以颞下颌关节（TMJ）和下颌肌肉功能障碍为特征的疾病，错颌是其重要的危险因素。我们最近发现，实验性单侧前交叉咬合（UAC）通过一个涉及牙周本体感觉、三叉神经中脑核（Vme）和三叉神经运动核（Vmo）的回路产生咬肌过度活跃。焦虑是TMD患者常见的并发症。外侧缰（LHb）参与情绪调节，并直接投射到Vme。因此，本研究考察了UAC是否促进了从LHb到Vme的兴奋性输入，并随后促进了大鼠的焦虑样行为。通过电生理记录、水疱性谷氨酸转运蛋白-2 (VGLUT2) mRNA表达和焦虑样行为的测量来评估LHb的激活。通过Vme神经元的电生理记录和VGLUT2蛋白密度的局部变化来评估LHb活性对Vme的影响。UAC在模型大鼠中产生焦虑，并增加LHb的神经元活动。LHb中VGLUT2 mRNA表达也升高。此外，在小白蛋白（PV）标记的Vme神经元上观察到vglut2阳性钮扣。VGLUT2蛋白在Vme中的表达也明显升高。值得注意的是，在LHb中注射VGLUT2靶向shRNA降低了Vme中VGLUT2蛋白的表达，减弱了uac相关的焦虑样行为，减弱了Vme神经元的电生理变化。综上所述，我们发现UAC激活LHb神经元以及牙周本体感受通路，为Vme提供兴奋输入并产生焦虑。这些发现为抑制LHb活性以减轻TMD的生理和心理影响提供了理论依据。
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.