title: 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 are 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.
authors.affiliation: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Smittkamp
authors.affiliation: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Spalding
authors.affiliation: The Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Brown
authors.affiliation: The Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Yeh
authors.affiliation: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States; The Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, United States. Electronic address: jstanford@kumc.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Stanford
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018737:Hand Strength / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008822:Mice, Transgenic; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D014059:Tongue / Q000502:physiology*
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: Amyotrophic; Bulbar; Cluster analysis; Preclinical models; Spinal; Survival