Immunoautoradiographic analysis of NMDA receptor subunits and associated postsynaptic density proteins in the brain of dyskinetic MPTP-treated common marmosets.
l-3,4-dihydroxyphenylalanine methyl ester (l-DOPA)-induced dyskinesia in Parkinson's disease may result from aberrant glutamatergic stimulation of the striatum due to synaptic plasticity in the motor cortex or striatum as a consequence of adaptation of striatal output pathways. This might result from changes in NMDA receptor subunit or NMDA receptor associated postsynaptic density (PSD) scaffold protein expression. Using immunoautoradiography the expression levels of NR1 and NR2B subunits of the NMDA receptor and the postsynaptic density scaffold proteins, PSD-95, PSD-93, and neurofilament light (NFL) were examined in normal common marmosets (Callithrix jacchus) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned animals that exhibited high or low levels of l-DOPA-induced dyskinesia. Brains from MPTP-lesioned animals that were not primed for l-DOPA-induced dyskinesia were not included in this study. No alterations in the NR1 NMDA receptor subunit were observed. The NR2B NMDA receptor subunit was increased in caudal caudate nucleus and putamen, hippocampus, cingulate motor area (CMA), supplementary motor area (SMA) and dorsal primary motor cortex (dMI) of highly dyskinetic MPTP-lesioned marmosets, but not in animals with low levels of dyskinesia. PSD-93 was decreased in the globus pallidus of marmosets with high and low levels of dyskinesia and increased in the CMA, SMA and dMI of highly dyskinetic marmosets. PSD-95 was increased in the SMA of highly dyskinetic marmosets, but not in animals with low dyskinesia. NFL expression was elevated in the SMA and dorsal and ventral MI of highly dyskinetic marmosets. These results suggest that l-DOPA treatment of MPTP-lesioned marmosets can affect glutamatergic systems and indicate that altered NMDA receptor function may relate to dyskinesia.
Hurley
M J
MJ
Neurodegenerative Diseases Research Group, Pharmaceutical Sciences Division, School of Health and Life Sciences, King's College, London, SE1 1UL, UK. michael.j.hurley@kcl.ac.uk
Jackson
M J
MJ
Smith
L A
LA
Rose
S
S
Jenner
P
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002144:Callithrix; D003952:Diagnostic Imaging / Q000379:methods; D000076122:Disks Large Homolog 4 Protein; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015592:Immunoradiometric Assay / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000978:Antiparkinson Agents; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C044882:neurofilament protein L; C033652:postsynaptic density proteins; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase