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Neurochemical Research

, Volume 31, Issue 11, pp 1337–1347 | Cite as

Changes in Subcellular Distribution and Phosphorylation of GluR1 in Lesioned Striatum of 6-Hydroxydopamine-Lesioned and l-dopa-Treated Rats

  • Maowen Ba
  • Min Kong
  • Hongqi Yang
  • Guozhao Ma
  • Guoqiang Lu
  • Shengdi Chen
  • Zhenguo Liu
Original Paper

Abstract

Recent evidence has linked striatal amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor function to the adverse effects of long-term dopaminergic treatment in Parkinson’s disease. The phosphorylation of AMPA subunit, GluR1, reflects AMPA receptor activity. To determine whether serine phosphorylation of GluR1 subunit by activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to the process, we examined the effects of unilateral nigrostriatal depletion with 6-hydroxydopamine and subsequent l-dopa treatment on motor responses and phosphorylation states. Three weeks of l-dopa administration to rats shortened the duration of the rotational response. We found a significant reduction in the abundance of both phosphorylated GluR1 at serine-831 site (pGluR1S831) and GluR1 in the cell plasma membrane of lesioned striatum. Chronic treatment of lesioned rats with l-dopa markedly upregulated the phosphorylation of GluR1 in lesioned striatum with a concomitant normalization of the plasma membrane GluR1 abundance, which lasted at least 1 day after withdrawal of chronic l-dopa treatment. Our immunostaining data showed that these changes were confined to parvalbumin-positive neurons where GluR1 subunits are exclusively expressed. Both the altered motor response duration and the degree of pGluR1S831 were attenuated by the intrastriatal administration of CaMKII inhibitor KN-93. These findings suggest that activation of CaMKII contributes to both development and maintenance of motor response duration alterations, through a mechanism that involves an increase in pGluR1S831 within parvalbumin-positive neurons.

Keywords

GluR1 Phosphorylation CaMKII Parvalbumin l-dopa PD 

Notes

Acknowledgments

This study was supported by a project sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry and the Post-Project of Excellent Young Medical Person of Xihhua Hospital of Shanghai, China.

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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Maowen Ba
    • 1
  • Min Kong
    • 1
  • Hongqi Yang
    • 2
  • Guozhao Ma
    • 3
  • Guoqiang Lu
    • 2
  • Shengdi Chen
    • 2
  • Zhenguo Liu
    • 1
  1. 1.Department of Neurology, Xinhua HospitalShanghai Jiaotong University School of MedicineShanghaiPeople’s Republic of China
  2. 2.Department of Neurology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiPeople’s Republic of China
  3. 3.Department of Neurology, Shandong Provincial HospitalShandong University School of MedicineShandongPeople’s Republic of China

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