Pleiotrophin receptor RPTP‐ζ/β expression is up‐regulated by l‐DOPA in striatal medium spiny neurons of parkinsonian rats

• Published in: Journal of neurochemistry Vol. 107; no. 2; pp. 443 - 452
• Main Authors: Ferrario, Juan Esteban, Rojas‐Mayorquín, Argelia Esperanza, Saldaña‐Ortega, Marisa, Salum, Cristiane, Gomes, Margarete Zanardo, Hunot, Stéphane, Raisman‐Vozari, Rita
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2008; Blackwell
• Subjects: Analysis of Variance; Animals; Antiparkinson Agents - pharmacology; Antiparkinson Agents - therapeutic use; Behavior, Animal - drug effects; Biological and medical sciences; Corpus Striatum - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Drug Interactions; Hematologic and hematopoietic diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Levodopa - pharmacology; Levodopa - therapeutic use; l‐DOPA; Male; Medical sciences; Neurology; Neurons - classification; Neurons - drug effects; Neurons - metabolism; Oxidopamine; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - pathology; Parkinson’s disease; plasticity; pleiotrophin; quantitative RT‐PCR; Rats; Rats, Wistar; receptor protein tyrosine phosphatase zeta/beta; Receptor-Like Protein Tyrosine Phosphatases, Class 5 - genetics; Receptor-Like Protein Tyrosine Phosphatases, Class 5 - metabolism; RNA, Messenger - metabolism; Up-Regulation - drug effects; Parkinson's disease; Rat; Central nervous system; Phosphoric monoester hydrolases; Parkinson disease; Esterases; Encephalon; Lymphoproliferative syndrome; Plasticity; L-DOPA; quantitative RT-PCR; receptor protein tyrosine phosphatase zeta/beta; Degenerative disease; Biological receptor; Drug; Nervous system diseases; Enzyme; Rodentia; Pleiotrophin; Malignant hemopathy; Basal ganglion; Corpus striatum; Long term; Lymphoma; Protein; Cerebral disorder; Vertebrata; Heparin affin regulatory peptide; Mammalia; Neuron; Treatment; Central nervous system disease; Hydrolases; Lesion; Immunofluorescence; Cancer; Extrapyramidal syndrome; Protein-tyrosine-phosphatase
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05640.x

l‐DOPA is still the drug of choice to treat Parkinson’s disease although adverse side effects appear after several years of treatment. These are thought to be the consequence of plastic re‐arrangements of the nigrostriatal connections, such as sprouting of the dopaminergic terminals or post‐synaptic changes. Pleiotrophin, a trophic factor that we have shown to be up‐regulated in the striatum of parkinsonian rats after long‐term l‐DOPA treatment may play a role in these plastic changes. To determine whether one of the three known pleiotrophin receptors [N‐syndecan, receptor protein tyrosine phosphatase type zeta beta (RPTP‐ζ/β) and anaplastic lymphoma kinase] might be implicated in these putative plastic effects, we quantified their expression levels by real‐time RT‐PCR in the striatum and mesencephalon of rats with partial lesions of the nigrostriatal pathway undergoing l‐DOPA treatment. Both pleiotrophin and RPTP‐ζ/β expression was up‐regulated in the striatum but not in the mesencephalon of lesioned rats and RPTP‐ζ/β expression was even further increased by l‐DOPA. The levels of the RPTP‐ζ/β protein were also increased in the striatum of l‐DOPA‐treated lesioned rats. Immunofluorescence labeling showed the protein to be constitutively expressed in striatal medium spiny neurons, which are innervated by both the corticostriatal glutamatergic and nigrostriatal dopaminergic systems. RPTP‐ζ/β might therefore be implicated in the plastic changes triggered by l‐DOPA treatment and might merit further study as a potential candidate for Parkinon’s disease therapy.