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Immunoautoradiographic analysis of NMDA receptor subunits and associated postsynaptic density proteins in the brain of dyskinetic MPTP-treated common marmosets

Immunoautoradiographic analysis of NMDA receptor subunits and associated postsynaptic density proteins in the brain of dyskinetic MPTP-treated common marmosets
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.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Antiparkinson Agents, Blotting, Western, Brain, Callithrix, Diagnostic Imaging, Disks Large Homolog 4 Protein, Dyskinesia, Drug-Induced, Immunoradiometric Assay, Intracellular Signaling Peptides and Proteins, Levodopa, Membrane Proteins, Nerve Tissue Proteins, Neurofilament Proteins, Protein Subunits, Rats, Receptors, N-Methyl-D-Aspartate, Tyrosine 3-Monooxygenase, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
0953-816X
3240-3250
Hurley, M J
07b0180f-8e32-4ce1-8185-e046a42ef15a
Jackson, M J
7b16c63d-effe-47fc-a382-8e5c444a5df0
Smith, L A
55e306e2-5377-444a-8d12-2de274625784
Rose, S
232c2464-efc4-4b5b-a199-4f554a33b3c2
Jenner, P
785c25df-ec64-4181-b057-26dd31cd9d84
Hurley, M J
07b0180f-8e32-4ce1-8185-e046a42ef15a
Jackson, M J
7b16c63d-effe-47fc-a382-8e5c444a5df0
Smith, L A
55e306e2-5377-444a-8d12-2de274625784
Rose, S
232c2464-efc4-4b5b-a199-4f554a33b3c2
Jenner, P
785c25df-ec64-4181-b057-26dd31cd9d84

Hurley, M J, Jackson, M J, Smith, L A, Rose, S and Jenner, P (2005) Immunoautoradiographic analysis of NMDA receptor subunits and associated postsynaptic density proteins in the brain of dyskinetic MPTP-treated common marmosets. European Journal of Neuroscience, 21 (12), 3240-3250. (doi:10.1111/j.1460-9568.2005.04169.x).

Record type: Article

Abstract

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.

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More information

Published date: June 2005
Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Antiparkinson Agents, Blotting, Western, Brain, Callithrix, Diagnostic Imaging, Disks Large Homolog 4 Protein, Dyskinesia, Drug-Induced, Immunoradiometric Assay, Intracellular Signaling Peptides and Proteins, Levodopa, Membrane Proteins, Nerve Tissue Proteins, Neurofilament Proteins, Protein Subunits, Rats, Receptors, N-Methyl-D-Aspartate, Tyrosine 3-Monooxygenase, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 417221
URI: http://eprints.soton.ac.uk/id/eprint/417221
ISSN: 0953-816X
PURE UUID: 3631993a-b8a1-44b9-ba1c-160651766cf3

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Date deposited: 25 Jan 2018 17:30
Last modified: 15 Jan 2020 17:44

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