Changes in Subcellular Distribution and Phosphorylation of GluR1 in Lesioned Striatum of 6-Hydroxydopamine-Lesioned and l-dopa-Treated Rats |
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Authors: | Maowen Ba Min Kong Hongqi Yang Guozhao Ma Guoqiang Lu Shengdi Chen Zhenguo Liu |
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Affiliation: | (1) Department of Neurology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of China;(2) Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China;(3) Department of Neurology, Shandong Provincial Hospital, Shandong University School of Medicine, Shandong, 250021, People’s Republic of China |
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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.Maowen Ba and Min Kong are contributed equally to this work. |
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Keywords: | GluR1 Phosphorylation CaMKII Parvalbumin font-variant:small-caps" >l-dopa PD |
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