Pleiotrophin mediates the maturation of dopaminergic neurons in culture

FERRARIO, JUAN ESTEBAN; MOURLEVAT, SOPHIE; DEBEIR, THOMAS; DELBE, JEAN; CARUELLE, DANIELE; LEJEUNE, OLIVIER; DEPIENNE, CHRISTELLE; COURTY, JOSE; RAISMAN-VOZARI, RITA; RUBERG, MERLE

Innsbruck, Austria

Congreso; The 20th Biennial Meeting of the ISN; 2005

International Society for Neurochemistry

Pleiotrophin (PTN) is a secreted heparin-binding growth factor that is highly expressed during early postnatal brain development and is upregulated after experimental lesions in the hippocampus of adult animals. Recently we have found that it is overexpressed in the striatum of 6-OHDA lesioned rats treated for 6 months with levodopa. To understand better the mechanism of action of PTN on DA neurons, we plated mixed primary mesencephalic cultures in plates precoated with PTN. These neurons had more elaborate neurites than control cultures. The number of TH-positive neurons also increased 20-30% in cultures plated on PTN compared with control, but this was due to better adhesion of the cells to the wells, not better survival. Furthermore, by adding a neutralizing anti-PTN antibody to the culture medium, we showed that endogenous PTN is implicated in the initial, and cAMP-dependent enhancement of, differentiation of the dopaminergic neurons. By in situ hybridization, we showed that ptn is mainly expressed by astrocytes in the cultures, whereas double fluorescence immunocytochemistry revealed that the PTN protein and its receptors, syndecan 3 and RTPT-z/b, are found on all cell types, including dopaminergic neurons, supporting the hypothesis that PTN is a trophic factor for these cells. PTN itself, or together with other neurotropic factors, might therefore increase the benefit of cell-based therapies for patients with Parkinson’s Disease in which dopaminergic neurons degenerate.