title: Changes in subcellular distribution and phosphorylation of GluR1 in lesioned striatum of 6-hydroxydopamine-lesioned and l-dopa-treated rats.
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 Ca(2+)/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.
authors.affiliation: Department of Neurology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, People's Republic of China. zhenguoliu2006@163.com
authors.forename: Maowen
authors.initials: M
authors.lastname: Ba
authors.forename: Min
authors.initials: M
authors.lastname: Kong
authors.forename: Hongqi
authors.initials: H
authors.lastname: Yang
authors.forename: Guozhao
authors.initials: G
authors.lastname: Ma
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Lu
authors.forename: Shengdi
authors.initials: S
authors.lastname: Chen
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013565:Sympatholytics / Q000633:toxicity; D000096926:Benzenesulfonamides
chemical_list: D000978:Antiparkinson Agents; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D007980:Levodopa; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D018091:Receptors, AMPA; D013449:Sulfonamides; D013565:Sympatholytics; C072105:KN 93; D000096926:Benzenesulfonamides