A Strength Endurance Exercise Paradigm Mitigates Deficits in Hypoglossal-Tongue Axis Function, Strength, and Structure in a Rodent Model of Hypoglossal Motor Neuron Degeneration.
A Strength Endurance Exercise Paradigm Mitigates Deficits in Hypoglossal-Tongue Axis Function, Strength, and Structure in a Rodent Model of Hypoglossal Motor Neuron Degeneration.
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DOI：
10.3389/fnins.2022.869592
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发表时间：
2022
影响因子：
4.3
通讯作者：
Lever, Teresa E.
中科院分区：
文献类型：
--
作者：
Murphy, Erika R.;Thompson, Rebecca;Osman, Kate L.;Haxton, Chandler;Brothers, Margaret;Lee, Li;Warncke, Kristen;Smith, Catherine L.;Keilholz, Amy N.;Hamad, Ali;Golzy, Mojgan;Bunyak, Filiz;Ma, Lixin;Nichols, Nicole L.;Lever, Teresa E.
舌头在吞咽过程中起着至关重要的作用，损伤可导致吞咽困难，特别是运动神经元疾病（mnd）导致舌下-舌轴变性（如肌萎缩性侧索硬化和进行性球麻痹）。本研究利用我们先前建立的诱导啮齿动物吞咽困难模型，该模型是由于舌下-舌轴的靶向变性引起的。该模型是通过将霍乱毒素B结合皂苷（cbb - sap）注射到舌底的颏舌肌，并通过舌下神经逆行运输到舌下核（XII），舌下神经是舌的唯一运动控制。我们的目的是研究高重复/低阻力舌运动对四组雄性大鼠舌功能、力量和结构的影响：(1)对照组+假性运动（n = 13）；(2)对照+锻炼（n = 10）；(3) CTB-SAP +假练习（n = 13）；(4) CTB-SAP +运动（n = 12）。对于每一组，在舌头注射后的第4天和第6天，将一个定制的喷嘴放置在家庭笼中过夜，该喷嘴具有可调节的舔舐力要求，以便液体进入。对于两个假运动组，舔力需求可以忽略不计。对于两个运动组，舔舐力要求设定为比单个大鼠的最大自愿舔舐力大40%。在运动暴露后，我们评估了对舌下-舌轴功能（通过视频透视）、强度（通过力舔计）和结构（通过脑干和舌头的磁共振成像（MRI））的影响。结果显示，模拟运动的CTB-SAP大鼠在舔食率、吞咽时间和舔食力方面存在显著缺陷。运动CTB-SAP大鼠的舔舐率和舔舐力保持不变；然而，吞咽时机缺陷仍然存在。MRI显示舌下-舌轴相应的退行性改变，通过舌头运动减轻。这些共同的发现表明，在我们的模型中，高重复/低阻力的舌头运动是一种安全有效的治疗方法，可以预防/减少舌下-舌轴变性的迹象。下一步是利用我们的大鼠模型来优化运动剂量参数，并研究相应的治疗作用机制，以便将来转化为MND临床试验。
The tongue plays a crucial role in the swallowing process, and impairment can lead to dysphagia, particularly in motor neuron diseases (MNDs) resulting in hypoglossal-tongue axis degeneration (e.g., amyotrophic lateral sclerosis and progressive bulbar palsy). This study utilized our previously established inducible rodent model of dysphagia due to targeted degeneration of the hypoglossal-tongue axis. This model was created by injecting cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue base for retrograde transport to the hypoglossal (XII) nucleus via the hypoglossal nerve, which provides the sole motor control of the tongue. Our goal was to investigate the effect of high-repetition/low-resistance tongue exercise on tongue function, strength, and structure in four groups of male rats: (1) control + sham exercise (n = 13); (2) control + exercise (n = 10); (3) CTB-SAP + sham exercise (n = 13); and (4) CTB-SAP + exercise (n = 12). For each group, a custom spout with adjustable lick force requirement for fluid access was placed in the home cage overnight on days 4 and 6 post-tongue injection. For the two sham exercise groups, the lick force requirement was negligible. For the two exercise groups, the lick force requirement was set to ∼40% greater than the maximum voluntary lick force for individual rats. Following exercise exposure, we evaluated the effect on hypoglossal-tongue axis function (via videofluoroscopy), strength (via force-lickometer), and structure [via Magnetic Resonance Imaging (MRI) of the brainstem and tongue in a subset of rats]. Results showed that sham-exercised CTB-SAP rats had significant deficits in lick rate, swallow timing, and lick force. In exercised CTB-SAP rats, lick rate and lick force were preserved; however, swallow timing deficits persisted. MRI revealed corresponding degenerative changes in the hypoglossal-tongue axis that were mitigated by tongue exercise. These collective findings suggest that high-repetition/low-resistance tongue exercise in our model is a safe and effective treatment to prevent/diminish signs of hypoglossal-tongue axis degeneration. The next step is to leverage our rat model to optimize exercise dosing parameters and investigate corresponding treatment mechanisms of action for future translation to MND clinical trials.
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影响因子：
3.4
作者：
Lind LA;Lever TE;Nichols NL
通讯作者：
Nichols NL
影响因子：
3.9
作者：
Jasiewicz, Barbara;Klimiec, Ewa;Guzdek, Piotr;Kolaszczynski, Grzegorz;Piekarski, Jacek;Zaraska, Krzysztof;Potaczek, Tomasz
通讯作者：
Potaczek, Tomasz
影响因子：
2
作者：
Argolo, Natalie;Sampaio, Marilia;Nobrega, Ana Caline
通讯作者：
Nobrega, Ana Caline
影响因子：
2.9
作者：
Cullins, Miranda J.;Connor, Nadine P.
通讯作者：
Connor, Nadine P.
影响因子：
3.3
作者：
Alves, Pedro
通讯作者：
Alves, Pedro