Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model

Neural stem cell transplantation therapy was developed for replacing lost or damaged neural cells for the neurodegenerative disease, including Parkinson's disease (PD), in which dopaminergic neuron cells are lost. The growth factor, neurotrophin-3(NT-3), has been shown to promote neuroregeneration, differentiation and migration during brain development. In this report, we construct rat neural stem cells that express neurotrophin-3 endogenously (rNSC-NT3) and transplant them into 6-hydroxydopa mine (6-OHDA)-treated Parkinsonian rats. Molecular approaches including quantitative real time PCR, Western blot and immunocytochemistry were used to identify the expression of NT-3 and the differentiation of planted cells. Behavioral recover was also tested. The result indicated that combined treatment of neurotrophin-3 gene and neural stem cells had a functional impact on reversing the main symptoms of the Parkinson's disease that significantly reduced apomorphine-induced rotational asymmetry and improved spatial learning ability. The rNSCs-NT3 is able to differentiate into dompaminergic neuron in the ventral tegmental area (VTA) and the medial forebrain bundle (MFB), and migrated around the lesion site. Endogenous expressed NT-3 exerts induction and trophic effects on neural stem cells. The rNSCs-NT3 showed higher activity than the rNSCs in regenerating tyrosine hydroxylase positive cell numbers and migrating distance, behavior improving in this dopa-deficit rat model. These findings suggest that the neural stem cells expressed NT-3 endogenously would be a better graft candidate for the treatment of Parkinson's disease. (C) 2008 Elsevier B.V. All rights reserved.