Document Detail

Abnormal cerebellar signaling induces dystonia in mice.
MedLine Citation:
PMID:  12196606     Owner:  NLM     Status:  MEDLINE    
Dystonia is a relatively common neurological syndrome characterized by twisting movements or sustained abnormal postures. Although the basal ganglia have been implicated in the expression of dystonia, recent evidence suggests that abnormal cerebellar function is also involved. In these studies, a novel mouse model was developed to study the role of the cerebellum in dystonia. Microinjection of low doses of kainic acid into the cerebellar vermis of mice elicited reliable and reproducible dystonic postures of the trunk and limbs. The severity of the dystonia increased linearly with kainate dose. Kainate-induced dystonia was blocked by the glutamatergic antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide and reproduced by domoic acid microinjection, suggesting that the induction of dystonia is dependent on glutamatergic activation in this model. The abnormal movements were not associated with kainate-induced seizures, because EEG recordings showed no epileptiform activity during the dystonic events. Neuronal activation, as assessed by in situ hybridization for c-fos, revealed c-fos mRNA expression in the cerebellum, locus ceruleus, and red nucleus. In contrast, regions associated with epileptic seizures, such as the hippocampus, did not exhibit increased c-fos expression after cerebellar kainate injection. Furthermore, in transgenic mice lacking Purkinje cells, significantly less dystonia was induced after kainic acid injection, implicating Purkinje cells and the cerebellar cortex in this model of dystonia. Together, these data suggest that abnormal cerebellar signaling produces dystonia and that the cerebellum should be considered along with the basal ganglia in the pathophysiology of this movement disorder.
Carolyn E Pizoli; H A Jinnah; Melvin L Billingsley; Ellen J Hess
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  22     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-27     Completed Date:  2002-09-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7825-33     Citation Subset:  IM    
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
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MeSH Terms
Action Potentials
Behavior, Animal / drug effects
Cerebellum / drug effects,  pathology,  physiopathology*
Disease Models, Animal*
Dose-Response Relationship, Drug
Dystonia / chemically induced,  etiology*,  pathology,  physiopathology*
Electroencephalography / drug effects
Excitatory Amino Acid Agonists / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Glutamic Acid / metabolism
Kainic Acid
Mice, Inbred C57BL
Mice, Transgenic
Organ Specificity / drug effects
Proto-Oncogene Proteins c-fos / biosynthesis,  genetics
Purkinje Cells / drug effects
RNA, Messenger / biosynthesis
Reproducibility of Results
Severity of Illness Index
Synaptic Transmission / drug effects
Grant Support
Reg. No./Substance:
0/Excitatory Amino Acid Agonists; 0/Excitatory Amino Acid Antagonists; 0/Proto-Oncogene Proteins c-fos; 0/RNA, Messenger; 487-79-6/Kainic Acid; 56-86-0/Glutamic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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