RGD Reference Report - RGS4 is involved in the generation of abnormal involuntary movements in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease. - Rat Genome Database

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RGS4 is involved in the generation of abnormal involuntary movements in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease.

Authors: Ko, Wai Kin D  Martin-Negrier, Marie-Laure  Bezard, Erwan  Crossman, Alan R  Ravenscroft, Paula 
Citation: Ko WK, etal., Neurobiol Dis. 2014 Oct;70:138-48. doi: 10.1016/j.nbd.2014.06.013. Epub 2014 Jun 24.
RGD ID: 13524515
Pubmed: PMID:24969021   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nbd.2014.06.013   (Journal Full-text)

Regulators of G-protein signalling (RGS) proteins are implicated in striatal G-protein coupled receptor (GPCR) sensitisation in the pathophysiology of l-DOPA-induced abnormal involuntary movements (AIMs), also known as dyskinesia (LID), in Parkinson's disease (PD). In this study, we investigated RGS protein subtype 4 in the expression of AIMs in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of LID. The effects of RGS4 antisense brain infusion on the behavioural and molecular correlates of l-DOPA priming in 6-OHDA-lesioned rats were assessed. In situ hybridisation revealed that repeated l-DOPA/benserazide treatment caused an elevation of RGS4 mRNA levels in the striatum, predominantly in the lateral regions. The increased expression of RGS4 mRNA in the rostral striatum was found to positively correlate with the behavioural (AIM scores) and molecular (pre-proenkephalin B, PPE-B expression) markers of LID. We found that suppressing the elevation of RGS4 mRNA in the striatum by continuous infusion of RGS4 antisense oligonucleotides, via implanted osmotic mini-pumps, during l-DOPA priming, reduced the induction of AIMs. Moreover, ex vivo analyses of the rostral dorsolateral striatum showed that RGS4 antisense infusion attenuated l-DOPA-induced elevations of PPE-B mRNA and dopamine-stimulated [(35)S]GTPγS binding, a marker used for measuring dopamine receptor super-sensitivity. Taken together, these data suggest that (i) RGS4 proteins play an important pathophysiological role in the development and expression of LID and (ii) suppressing the elevation of RGS4 mRNA levels in l-DOPA priming attenuates the associated pathological changes in LID, dampening its physiological expression. Thus, modulating RGS4 proteins could prove beneficial in the treatment of dyskinesia in PD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RGS4HumanDrug-Induced Dyskinesia treatmentISORgs4 (Rattus norvegicus)associated with Parkinsonian DisordersRGD 
Rgs4RatDrug-Induced Dyskinesia treatmentIMP associated with Parkinsonian DisordersRGD 
Rgs4MouseDrug-Induced Dyskinesia treatmentISORgs4 (Rattus norvegicus)associated with Parkinsonian DisordersRGD 

Objects Annotated

Genes (Rattus norvegicus)
Rgs4  (regulator of G-protein signaling 4)

Genes (Mus musculus)
Rgs4  (regulator of G-protein signaling 4)

Genes (Homo sapiens)
RGS4  (regulator of G protein signaling 4)


Additional Information