Relationships between tongue motility, grip force, and survival in SOD1-G93A rats

Abstract

Most preclinical studies of amyotrophic lateral sclerosis (ALS) have focused on spinal symptoms, despite the importance of bulbar deficits in progression of the disease. We sought to determine how bulbar deficits related to spinal deficits and survival in the SOD1-G93A rat model of ALS. We examined forelimb and hindlimb grip force and tongue motility in SOD1-G93A rats using statistical cluster analysis. Decrements in forelimb grip force, hindlimb grip force, and tongue motility were used to cluster affected rats into groups. The analysis clustered one group that exhibited primarily forelimb deficits (forelimb group) and a second group that exhibited forelimb and tongue motility deficits (forelimb + bulbar group). The analysis did not identify a distinct hindlimb phenotype group because all SOD1-G93A rats exhibited deficits in hindlimb grip force. Rats in the forelimb + bulbar group exhibited earlier and greater forelimb deficits, and earlier mortality than rats without bulbar deficits. Hindlimb deficits were similar in both groups. There was a significant correlation between forelimb grip force and tongue motility deficits, but not between forelimb and hindlimb deficits. These data extend clinical findings of a more rapid disease progression in individuals with bulbar symptoms to the SOD1-G93A rat model of ALS.

Effects of Tongue Force Training on Bulbar Motor Function in the Female SOD1-G93A Rat Model of Amyotrophic Lateral Sclerosis

“…We previously reported heterogeneity with regard to tongue motility deficits in SOD1-G93A rats. 8 Despite exacerbating these deficits, our tongue force training regimen did not influence their presence in the SOD1-G93A rats in the current study (ie, the number of rats exhibiting bulbar deficits did not differ between the trained and untrained groups). This is interesting because it suggests that whereas focal strength training of a cranial muscle during the presymptomatic phase does not produce a bulbar phenotype, it can exacerbate the phenotype.…”

“…Also like the human disease, SOD1-G93A rats exhibit heterogeneity with regard to spinal and bulbar deficits 7 . We reported tongue motility deficits in this model 7 and found that these deficits are related to survival 8 . Because of the greater incidence of bulbar deficits in females 9 , we divided female SOD1-G93A rats and healthy wildtype littermate controls into a training group and a control group.…”

“…We previously reported heterogeneity with regard to tongue motility deficits in SOD1-G93A rats 8 . Despite exacerbating these deficits, our tongue force training regimen did not influence their presence in the SOD1-G93A rats in the current study (i.e., the number of rats exhibiting bulbar deficits did not differ between the trained and untrained groups).…”

“…We have reported tongue motility deficits in both the SOD1-G93A mouse and rat models of ALS 7,8,13 . Our finding that these deficits were exacerbated by tongue force training was surprising.…”

“…At 4 months of age, rats were gradually water restricted and placed into individual customized Gerbrands operant chambers as described below and in our recent studies. 7,8 Testing began when rats were presymptomatic (body weight was still increasing) at 19 weeks of age and continued through late stage for each rat until a humane end point was reached. End point was defined as visible limb paralysis.…”