Pleiotrophin is expressed in the rat adult striatum and mediates the differentiation of dopaminergic neurons in culture

RAISMAN-VOZARI R; TARAVINI IR; FERRARIO JE; MOURLEVAT S; DEBEIR T; DELBE J; COURTY J; GINESTET L; MURER MG; RUBERG M; GERSHANIK O

Viena, Austria

Congreso; The Federation of European Neuroscience Societies, Forum 2006; 2006

The Federation of European Neuroscience Societies

Pleiotrophin (PTN) is a secreted heparin-binding growth factor that is highly expressed during early postnatal brain development. We have found PTN overexpressed in the striatum of 6-OHDA lesioned rats treated with levodopa, a model were we have also shown the recovery of striatal dopaminergic (DA) nerve terminals. Because striatal PTN can provide trophic support to DA neurons, we analyzed the cellular types containing PTN protein in the striatum of adult rats. Using fluorescent double immunolabeling we found PTN to co-localize with a neuronal nuclei marker but not with glial marker. The number, distribution, and morphology of the PTN-immunolabeled cells suggested that they were interneurons. Double-immunolabeling showed that ~40% of the PTN-immunolabeled neurons contained nitric oxide synthase or somatostatin and ~60% expressed the vesicular acetylcholine transporter, supporting that they were GABAergic nitric oxide synthase /somatostatin-containing neurons and cholinergic interneurons. PTN enhances neurite outgrowth in cultures and has been shown to be involved in axonal guidance. We investigated whether PTN affects either the differentiation and/or the survival of DA neurons. Using primary cultures of mesencephalon we observed that the number of TH-positive neurons increased 20-30% in cultures grown in the presence of PTN.The addition of cyclic AMP to the culture medium prevents neuronal death and increases the state of differentiation of DA neurons. The immunoneutralization of PTN with an specific antibody added to the culture medium interfere with this process. We found that PTN is implicated in the initial and cAMP-dependent enhancement of the differentiation of the DA neurons. Further work is necessary to determine if PTN from striatal interneurons can provide trophic support to DA neurons.