A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis
A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis
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DOI：
10.1007/s00455-009-9232-1
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发表时间：
2010-06-01
期刊：
影响因子：
2.6
通讯作者：
Murashov, Alexander K.
中科院分区：
文献类型：
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作者：
Lever, Teresa E.;Simon, Emmanuelle;Murashov, Alexander K.
我们最近发现SOD1-G93A转基因小鼠是肌萎缩性侧索硬化症（ALS）患者口腔期吞咽困难的合适模型。本研究的目的是确定它是否也可以作为咽期吞咽困难的模型。对SOD1-G93A转基因终末期小鼠（n = 9）和年龄匹配的野生型（WT）仔鼠（n = 12）进行电生理和组织学实验。与WT对照组（20 Hz）相比，转基因小鼠需要对喉上神经（SLN）施加两倍高的刺激频率（40 Hz）来唤醒吞咽；转基因雌性小鼠诱导吞咽所需的刺激频率显著高于转基因雄性小鼠（P < 0.05）。因此，两性均表现出咽吞咽困难的电生理证据，但女性的症状更为严重。神经退行性变（空泡）的组织学证据在咽部吞咽的代表性运动（歧义核）和感觉（孤束核）部分被发现，提示ALS咽部吞咽困难可能归因于运动和感觉病理。此外，本研究结果表明，感觉刺激方法可能促进ALS患者的吞咽功能。
We recently established that the SOD1-G93A transgenic mouse is a suitable model for oral-stage dysphagia in amyotrophic lateral sclerosis (ALS). The purpose of the present study was to determine whether it could serve as a model for pharyngeal-stage dysphagia as well. Electrophysiological and histological experiments were conducted on end-stage SOD1-G93A transgenic mice (n = 9) and age-matched wild-type (WT) littermates (n = 12). Transgenic mice required a twofold higher stimulus frequency (40 Hz) applied to the superior laryngeal nerve (SLN) to evoke swallowing compared with WT controls (20 Hz); transgenic females required a significantly higher (P < 0.05) stimulus frequency applied to the SLN to evoke swallowing compared with transgenic males. Thus, both sexes demonstrated electrophysiological evidence of pharyngeal dysphagia but symptoms were more severe for females. Histological evidence of neurodegeneration (vacuoles) was identified throughout representative motor (nucleus ambiguus) and sensory (nucleus tractus solitarius) components of the pharyngeal stage of swallowing, suggesting that pharyngeal dysphagia in ALS may be attributed to both motor and sensory pathologies. Moreover, the results of this investigation suggest that sensory stimulation approaches may facilitate swallowing function in ALS.