Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study examined the effect of a subchronic systemic administration of the glutamate metabotropic mGluR5 receptor antagonist MPEP on l-DOPA-induced dyskinesias and striatal gene expression in adult rats with a unilateral 6-OHDA lesion of dopamine neurons. The daily systemic administration of l-DOPA for 2 weeks induced a gradual increase in limb dyskinesia and axial dystonia. The subchronic systemic co-administration of MPEP reduced the severity of limb dyskinesia and axial dystonia over the whole duration of l-DOPA treatment. Subchronic l-DOPA administration was paralleled by a significant increase in mRNA levels of the two isoforms of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67 and GAD65) and preprodynorphin (PPD). Single cell analysis on emulsion radioautographs indicated that l-DOPA-induced increases in GAD67 occurred predominantly in preproenkephalin-unlabeled striatonigral and, to a lesser extent, in preproenkephalin-labeled striatopallidal neurons. MPEP completely reversed the effects of l-DOPA on GAD67 and reduced the increases in GAD65 and PPD mRNA levels in striatonigral neurons. MPEP also reversed the small l-DOPA-induced increase in GAD67 mRNA levels in striatopallidal neurons. Altogether, the findings support the idea that the relative efficacy of mGluR5 receptor antagonists to oppose l-DOPA-induced abnormal involuntary movements involves an ability to oppose increases in GAD gene expression and GABA-mediated signaling in striatonigral and striatopallidal neurons. The results also confirm the potential usefulness of antagonists of mGluR5 receptors as adjuncts in the treatment of l-DOPA-induced dyskinesia in patients with Parkinson's disease.
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PMID:Metabotropic glutamate mGluR5 receptor blockade opposes abnormal involuntary movements and the increases in glutamic acid decarboxylase mRNA levels induced by l-DOPA in striatal neurons of 6-hydroxydopamine-lesioned rats. 1966 May 28

High levels of bilirubin in infants can cause kernicterus, which includes basal ganglia damage and dystonia. Stem cell transplantation may be an effective treatment for this disease. In this study, we transplanted human neural progenitor cells differentiated toward propriospinal interneurons into the striatum of 20-day-old spontaneously jaundiced (jj) Gunn rats and nonjaundiced (Nj) littermates. Using immunohistochemical methods, we found that grafted cells survived and grew fibers in jj and Nj brains 3 weeks after transplantation. Grafted cells had a higher survival rate in jj than in Nj brains, suggesting that slightly elevated bilirubin may protect graft survival due to its antioxidative and immunosuppressive effects. Despite their survival, only a small portion of grafted neurons expressed GAD-6 or ChAT, which mark GABAergic and cholinergic neurons, respectively, and are the cells that we are attempting to replace in kernicterus. Thus, NPCs containing large populations of GABAergic and cholinergic neurons should be used for further study in this field.
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PMID:Fate of Neural Progenitor Cells Transplanted Into Jaundiced and Nonjaundiced Rat Brains. 2815 18

Movement disorders are a prominent and common feature in many autoantibody-associated neurological diseases, a group of potentially treatable conditions that can mimic infectious, metabolic or neurodegenerative disease. Certain movement disorders are likely to associate with certain autoantibodies; for example, the characteristic dyskinesias, chorea and dystonia associated with NMDAR antibodies, stiff person spectrum disorders with GAD, glycine receptor, amphiphysin or DPPX antibodies, specific paroxysmal dystonias with LGI1 antibodies, and cerebellar ataxia with various anti-neuronal antibodies. There are also less-recognized movement disorder presentations of antibody-related disease, and a considerable overlap between the clinical phenotypes and the associated antibody spectra. In this review, we first describe the antibodies associated with each syndrome, highlight distinctive clinical or radiological 'red flags', and suggest a syndromic approach based on the predominant movement disorder presentation, age, and associated features. We then examine the underlying immunopathophysiology, which may guide treatment decisions in these neuroimmunological disorders, and highlight the exceptional interface between neuronal antibodies and neurodegeneration, such as the tauopathy associated with IgLON5 antibodies. Moreover, we elaborate the emerging pathophysiological parallels between genetic movement disorders and immunological conditions, with proteins being either affected by mutations or targeted by autoantibodies. Hereditary hyperekplexia, for example, is caused by mutations of the alpha subunit of the glycine receptor leading to an infantile-onset disorder with exaggerated startle and stiffness, whereas antibodies targeting glycine receptors can induce acquired hyperekplexia. The spectrum of such immunological and genetic analogies also includes cerebellar ataxias and some encephalopathies. Lastly, we discuss how these pathophysiological considerations could reflect on possible future directions regarding antigen-specific immunotherapies or targeting the pathophysiological cascades downstream of the antibody effects.
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PMID:Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. 2905 77