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

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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.

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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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Authors and Affiliations

  1. Department of Neurology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of China

    Maowen Ba, Min Kong & Zhenguo Liu

  2. Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China

    Hongqi Yang, Guoqiang Lu & Shengdi Chen

  3. Department of Neurology, Shandong Provincial Hospital, Shandong University School of Medicine, Shandong, 250021, People’s Republic of China

    Guozhao Ma

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  1. Maowen Ba
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  2. Min Kong
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Correspondence to Zhenguo Liu.

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Maowen Ba and Min Kong are contributed equally to this work.

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Ba, M., Kong, M., Yang, H. et al. Changes in Subcellular Distribution and Phosphorylation of GluR1 in Lesioned Striatum of 6-Hydroxydopamine-Lesioned and l-dopa-Treated Rats. Neurochem Res 31, 1337–1347 (2006). https://doi.org/10.1007/s11064-006-9177-9

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  • DOI: https://doi.org/10.1007/s11064-006-9177-9

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