RGD Reference Report - Intrastriatal injection of ionomycin profoundly changes motor response to l-DOPA and its underlying molecular mechanisms. - Rat Genome Database

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Intrastriatal injection of ionomycin profoundly changes motor response to l-DOPA and its underlying molecular mechanisms.

Authors: Han, Chao  Nie, Shuke  Chen, Guiqin  Ma, Kai  Xiong, Nian  Zhang, Zhentao  Xu, Yan  Wang, Tao  Papa, Stella M  Cao, Xuebing 
Citation: Han C, etal., Neuroscience. 2017 Jan 6;340:23-33. doi: 10.1016/j.neuroscience.2016.10.033. Epub 2016 Oct 19.
RGD ID: 13514053
Pubmed: PMID:27771532   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2016.10.033   (Journal Full-text)

Long-term l-DOPA treatment of Parkinson's disease is accompanied with fluctuations of motor responses and l-DOPA-induced dyskinesia (LID). Phosphorylation of the dopamine and c-AMP regulated phosphoprotein of 32kDa (DARPP-32) plays a role in the pathogenesis of LID, and thus dephosphorylation of this protein by activated calcineurin may help reduce LID. One important activator of calcineurin is the Ca2+ionophore ionomycin. Here, we investigated whether intrastriatal injection of ionomycin to hemiparkinsonian rats produced changes in l-DOPA responses including LID. We also analyzed the effects of ionomycin on key molecular mediators of LID. Results confirmed our hypothesis that ionomycin could downregulate the phosphorylation of DARPP32 at Thr-34 and reduce LID. Besides, ionomycin decreased two established molecular markers of LID, FosB/¿FosB and phosphorylated ERK1/2. Ionomycin also decreased the phosphorylation of three main subunits of the NMDA receptor, NR1 phosphorylated at ser896, NR2A phosphorylated at Tyr-1325, and NR2B phosphorylated at Tyr-1472. Furthermore, the anti-LID effect of striatally injected ionomycin was not accompanied by reduction of the antiparkinsonian action of l-DOPA. These data indicate that ionomycin largely interacts with striatal mechanisms that are critical to the l-DOPA motor response highlighting the role of protein dephosphorylation by calcineurin.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPP1R1BHumanDrug-Induced Dyskinesia treatmentISOPpp1r1b (Rattus norvegicus)associated with Parkinsonian DisordersRGD 
Ppp1r1bRatDrug-Induced Dyskinesia treatmentIDA associated with Parkinsonian DisordersRGD 
Ppp1r1bMouseDrug-Induced Dyskinesia treatmentISOPpp1r1b (Rattus norvegicus)associated with Parkinsonian DisordersRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r1b  (protein phosphatase 1, regulatory (inhibitor) subunit 1B)

Genes (Mus musculus)
Ppp1r1b  (protein phosphatase 1, regulatory inhibitor subunit 1B)

Genes (Homo sapiens)
PPP1R1B  (protein phosphatase 1 regulatory inhibitor subunit 1B)


Additional Information