Animal models of generalized dystonia.
Dystonia is a prevalent neurological disorder characterized by abnormal co-contractions of antagonistic muscle groups that produce twisting movements and abnormal postures. The disorder may be inherited, arise sporadically, or result from brain insult. Dystonia is a heterogeneous disorder because patients may exhibit focal or generalized symptoms associated with abnormalities in many brain regions including basal ganglia and cerebellum. Elucidating the pathogenic mechanisms underlying dystonia has therefore been challenging. Animal models of dystonia exhibit similar heterogeneity and are useful for understanding pathogenesis. The neurochemical and neurophysiological abnormalities in rodents with idiopathic generalized dystonia suggest that dysfunctional output from basal ganglia, cerebellum, or from multiple systems is the cause of motor dysfunction. Findings from drug- or toxin-induced dystonia in rodents and nonhuman primates mirror the genetic models. The parallels between dystonia in humans and animals suggest that the models will continue to prove useful in determining pathogenesis. Furthermore, detailed characterization of the existing models of dystonia and the development of new models hold promise for the identification of novel therapeutics.
Raike
Robert S
RS
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jinnah
H A
HA
Hess
Ellen J
EJ
D000818:Animals; D001480:Basal Ganglia Diseases / Q000235:genetics; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004421:Dystonia / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D051381:Rats