title: Expression and phosphorylation of glutamate receptor subunits and CaMKII in a mouse model of Parkinsonism.
abstract: Dopaminergic deficiency of the weaver mutant mouse is a valuable tool to further our understanding of Parkinson׳s disease (PD) pathogenesis since dopaminergic neurons of the nigrostriatal pathway undergo spontaneous and progressive cell death. In the present study we investigated the changes in protein expression and phosphorylation of glutamate receptor subunits and αCaMKII in weaver striatum at the end of the third and sixth postnatal month. Using immunoblotting, we found increased immunoreactivity levels of both GluN2A and GluN2B subunits of NMDA receptors and GluA1 subunit of AMPA receptors approximately from 75% to 110% in the 3-month-old weaver striatum compared to control. In the 6-month-old weaver striatum, no changes were detected in GluN2A and GluA1 immunoreactivity levels, whereas GluN2B showed a 21% statistically significant increase. Our results also indicated increased phospho-S1303 GluN2B in both 3 and 6 month-olds and increased phospho-S831 and -845 GluA1 in 3 month-old weaver striatum. However, these increases did not exceed the increases observed for total GluN2B and GluA1. Furthermore, our results showed increased immunoreactivity levels for phospho-T286 αCaMKII by approximately 180% in the 6 month-old weaver striatum, while total CaMKII immunoreactivity levels were not altered at either 3- or 6-month-old weaver. Our results suggest that distinct degrees of DA neuron degeneration differentially affect expression and phosphorylation of striatal glutamate receptors and αCaMKII. Findings on this genetic parkinsonian model suggest that striatal glutamatergic signaling may play an important role in synaptic plasticity and motor behavior that follow progressive and chronic dopamine depletion in PD with biochemical consequences beyond those seen in acute toxic models.
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, University of Patras, 26500 Patras, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Koutsokera
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, University of Patras, 26500 Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kafkalias
authors.affiliation: Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, 26500 Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Giompres
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, University of Patras, 26500 Patras, Greece.
authors.forename: Elias D
authors.initials: ED
authors.lastname: Kouvelas
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, University of Patras, 26500 Patras, Greece. Electronic address: mitsacos@upatars.gr.
authors.forename: Ada
authors.initials: A
authors.lastname: Mitsacos
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D008818:Mice, Neurologic Mutants; D020734:Parkinsonian Disorders / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
keywords: AMPA receptor; CaMKII; NMDA receptor; Parkinsonism; Protein phosphorylation; Weaver striatum