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The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model.
Brain Res Bull. 2011 Nov 25; 86(5-6):367-72.BR

Abstract

Chronic dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease (PD) often leads to abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia (LID), mediated by DA receptors. However, mechanisms underlying LID occurrence are still unclear. Regulator of G-protein signaling RGS9, a member of the RGS family of GTPase accelerating proteins, is expressed specifically in the striatum, has been reported participated in LID. L-DOPA-induced AIMs can be modeled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injection of L-DOPA. Herein, we compared the rotational responses and AIMs in 6-OHDA lesioned rats with L-DOPA/benserazide (10/2.5 mg/kg, once per day, i.p.) administration for 14 days whereas control animals received injections of saline. Furthermore, whether sub-chronic L-DOPA treatment impact RGS9 mRNA or protein expression in 6-OHDA lesion rats were also evaluated. As results shown, rotational behavior was not increased significantly, while an obvious AIMs were observed in rats with L-DOPA/benserazide (10/2.5mg/kg, i.p.) administration sub-chronically. In addition, expressions of RGS9 protein or mRNA analyzed by Western blot or real-time PCR with striatal extracts increased significantly after L-DOPA/benserazide. These data demonstrate that RGS9 expression can be modulated by sub-chronic L-DOPA/benserazide administration and increased RGS9 expression in striatum may be one of the reasons for the side effects such as dyskinesia induced by L-DOPA therapy.

Authors+Show Affiliations

Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Disease of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China. yinll913@126.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21963945

Citation

Yin, Lin-Lin, et al. "The Involvement of RGS9 in L-3,4-dihydroxyphenylalanine-induced Dyskinesias in Unilateral 6-OHDA Lesion Rat Model." Brain Research Bulletin, vol. 86, no. 5-6, 2011, pp. 367-72.
Yin LL, Geng XC, Zhu XZ. The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model. Brain Res Bull. 2011;86(5-6):367-72.
Yin, L. L., Geng, X. C., & Zhu, X. Z. (2011). The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model. Brain Research Bulletin, 86(5-6), 367-72. https://doi.org/10.1016/j.brainresbull.2011.09.016
Yin LL, Geng XC, Zhu XZ. The Involvement of RGS9 in L-3,4-dihydroxyphenylalanine-induced Dyskinesias in Unilateral 6-OHDA Lesion Rat Model. Brain Res Bull. 2011 Nov 25;86(5-6):367-72. PubMed PMID: 21963945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model. AU - Yin,Lin-Lin, AU - Geng,Xing-Chao, AU - Zhu,Xing-Zu, Y1 - 2011/09/24/ PY - 2011/09/16/received PY - 2011/09/19/accepted PY - 2011/10/4/entrez PY - 2011/10/4/pubmed PY - 2012/4/6/medline SP - 367 EP - 72 JF - Brain research bulletin JO - Brain Res Bull VL - 86 IS - 5-6 N2 - Chronic dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease (PD) often leads to abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia (LID), mediated by DA receptors. However, mechanisms underlying LID occurrence are still unclear. Regulator of G-protein signaling RGS9, a member of the RGS family of GTPase accelerating proteins, is expressed specifically in the striatum, has been reported participated in LID. L-DOPA-induced AIMs can be modeled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injection of L-DOPA. Herein, we compared the rotational responses and AIMs in 6-OHDA lesioned rats with L-DOPA/benserazide (10/2.5 mg/kg, once per day, i.p.) administration for 14 days whereas control animals received injections of saline. Furthermore, whether sub-chronic L-DOPA treatment impact RGS9 mRNA or protein expression in 6-OHDA lesion rats were also evaluated. As results shown, rotational behavior was not increased significantly, while an obvious AIMs were observed in rats with L-DOPA/benserazide (10/2.5mg/kg, i.p.) administration sub-chronically. In addition, expressions of RGS9 protein or mRNA analyzed by Western blot or real-time PCR with striatal extracts increased significantly after L-DOPA/benserazide. These data demonstrate that RGS9 expression can be modulated by sub-chronic L-DOPA/benserazide administration and increased RGS9 expression in striatum may be one of the reasons for the side effects such as dyskinesia induced by L-DOPA therapy. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/21963945/The_involvement_of_RGS9_in_l_34_dihydroxyphenylalanine_induced_dyskinesias_in_unilateral_6_OHDA_lesion_rat_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(11)00289-9 DB - PRIME DP - Unbound Medicine ER -