Expression of an Heparin-Binding Growth Associated Molecule (Pleiotrophin) by Striatal Interneurons and Nigral Dopaminergic Neurons

TARAVINI IR; FERRARIO JE; DELBE J; COURTY J; MURER MG; RAISMAN-VOZARI R; GERSHANIK O

New Orleans, Louisiana, USA

Congreso; 9th International Congress of Parkinson’s Disease and Movement Disorders; 2005

The Movement Disorders Society

Objective: To identify the different cellular types expressing Pleiotrophin (PTN) at the striatal and nigral (SN) levels. Background: Parkinson’s disease is characterized by a selective damage of the dopaminergic nigrostriatal pathway. Surviving neurons undergo both spontaneous and levodopa induced plastic changes. We have recently reported the finding of an increased expression of PTN in the striatum of rats with a unilateral 6-OHDA lesion of the nigrostriatal tract chronically treated with levodopa. Interestingly, recent reports have shown that PTN stimulates the differentiation of dopaminergic mesencephalic neurons in vitro. Methods and Results: By means of fluorescent double-immunolabeling we found PTN to colocalize with NeuN (neuronal marker) but not with GFAP (glial marker) both in the striatum and SN. In the SN, PTN colocalized with TH (a dopaminergic neuronal marker). At the striatal level, the number, distribution, and morphology of the PTN cholorimetric immunolabeled neurons was highly suggestive of an interneuronal localization. Double fluorescent immunolabeling of PTN with specific markers for interneuronal subpopulations at this level ruled out calretinin (+) and parvalbumin (+) GABAergic neurons. On the other hand ~42% of PTN immunolabeled neurons corresponded to GABAergic interneurons expressing nitric oxide synthase (NOS) and somatostatin (SST) (range 33-52%, n=3), while ~61%  of them expressed the vesicular acetylcholine transporter (range 60-62%, n=3). Correspondigly, ~15% of NOS/SST positive neurons, and ~74% of cholinergic interneurons expressed PTN. We also studied the distribution of the PTN receptor N-syndecan, and found it to colocalize with TH in the SN. Conclusions: Our results suggest PTN is either contained and/or released in vivo by both striatal interneurons and nigral dopaminergic neurons. This novel trophic factor would possibly mediate some of the plastic changes that the surviving dopaminergic nigrostriatal neurons undergo in the parkinsonian brain.