An Animal Model of Oral Dysphagia in Amyotrophic Lateral Sclerosis

Abstract

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 (approximately 110 days), and disease end-stage (approximately 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.

Histological Bulbar Manifestations in the ALS Rat

“…Importantly, however, our histological findings do align well with known disease findings in human ALS subjects [2,3,4]. In the current study, we observed a decreased number of neurons in the facial, hypoglossal, and trigeminal nuclei.…”

“…Almost all ALS patients develop some bulbar dysfunction attributed to degeneration of brainstem motor nuclei of cranial nerves V, VII, IX, X, and XII [2,3,4,5]. This degeneration results in functional deficits in muscles of the head, neck, and face that affect speech, swallowing, tongue coordination, and vocal cord function.…”

“…This model develops weakness at 100 days of age followed by paralysis and death at 140 days of age [8]. Moreover, various studies indicate that these mice are adequate models for bulbar-onset ALS, with decreased lick and mastication rates, and decreased pharyngeal muscle strength when compared to controls [2]. Recently, the SOD1-G93A rat has also gained popularity due its larger size, making it more amenable to testing novel surgical therapeutic options.…”

“…The SOD1-G93A transgenic mouse, based on the familial ALS-associated mutation in the Cu 2+ /Zn 2+ superoxide dismutase (SOD1) gene, is routinely used as an animal model for ALS [2,7]. This model develops weakness at 100 days of age followed by paralysis and death at 140 days of age [8].…”

Does the Goal Justify the Methods? Harm and Benefit in Neuroscience Research Using Animals

“…In this model, the onset of this neurological disease is characterized by weakness and tremors of hind limbs. Disease progression then leads to paralysis of hind limbs, accompanied by increased difficulty to eat, drink, and swallow, terminating in complete paralysis (Lever et al 2009(Lever et al , 2010. Mice die of respiratory failure due to paralysis of diaphragm (Solomon et al 2011).…”