An Animal Model of Oral Dysphagia in Amyotrophic Lateral Sclerosis
An Animal Model of Oral Dysphagia in Amyotrophic Lateral Sclerosis
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DOI：
10.1007/s00455-008-9190-z
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发表时间：
2009-06-01
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.;Gorsek, Ambre;Murashov, Alexander K.
对肌萎缩侧索硬化症(ALS)吞咽困难的潜在神经病理知之甚少；因此，有效的治疗方法仍然难以捉摸。通过在ALS研究中使用吞咽困难的动物模型，在理解和治疗ALS吞咽困难方面可能取得巨大进展；然而，目前还没有这样的动物模型。最合乎逻辑的候选是SOD1-G93A转基因小鼠，它是研究最广泛的ALS动物模型。为了研究SOD1-G93A转基因小鼠是否出现吞咽困难，根据后肢运动功能，在无症状(60d)、发病(约110d)和疾病末期(约140d)三个时间点对SOD1-G93A转基因小鼠(n=30)的口腔行为(舔和咀嚼)进行了评估。年龄匹配的非转基因窝产仔(n=30)作为对照。在每个时间点，转基因小鼠的舔舔和咀嚼频率都显著低于对照组(p<；0.05)。脑干的组织学分析显示，三叉神经核和舌下核有显著的神经变性(空泡化)，这两个关键运动成分参与咀嚼和舔食行为。这些结果证明了SOD1-G93A转基因小鼠口腔功能障碍的临床病理相关性，从而建立了SOD1-G93A转基因小鼠作为ALS口腔吞咽困难的真实动物模型。
Relatively little is known about the underlying neuropathology of dysphagia in amyotrophic lateral sclerosis (ALS); thus, effective treatments remain elusive. Tremendous progress toward understanding and treating dysphagia in ALS may be possible through the use of an animal model of dysphagia in ALS research; however, no such animal model currently exists. The most logical candidate to consider is the SOD1-G93A transgenic mouse, the most widely investigated animal model of ALS. To investigate whether this animal model develops dysphagia, oral behaviors (lick and mastication rates) of SOD1-G93A transgenic mice (n = 30) were evaluated at three time points based on hind limb motor function: asymptomatic (60 days), disease onset (similar to 110 days), and disease end-stage (similar to 140 days). Age-matched nontransgenic littermates (n = 30) served as controls. At each time point, lick and mastication rates were significantly lower (p < 0.05) for transgenic mice compared with controls. Histologic analysis of the brainstem showed marked neurodegeneration (vacuolation) of the trigeminal and hypoglossal nuclei, two key motor components involved in mastication and licking behaviors. These results demonstrate a clinicopathologic correlation of oral dysfunction in SOD1-G93A transgenic mice, thereby establishing the SOD1-G93A transgenic mouse as a bona fide animal model of oral dysphagia in ALS.