Abstract

Neural stem cell (NSC) transplantation has the potential to treat neurodegenerative diseases such as Parkinson's disease (PD). In this study, we investigated the effect of transplanted NSCs in a PD animal model. NSCs isolated from the subventricular zone (SVZ) of E14 rats were cultured in vitro to produce neurospheres, which were subsequently infected with recombinant adeno-associated virus (rAAV(2)) expressing enhanced green fluorescent protein (EGFP). The PD animal model was established by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of Sprague-Dawley rats. Once the model was established, EGFP-expressing NSCs were transplanted into the substantia nigra pars compacta (SNc) or striatum of PD rats. We found that NSCs transplanted into either site significantly reduced apomorphine-induced circling behavior of PD rats. Pathological analysis revealed that the EGFP-expressing NSCs could be detected at both injection sites at 1, 2 and 4 months after transplantation. SNc transplanted cells dispersed within the SNc with a significant portion differentiated into tyrosine hydroxylase-positive neurons. Whereas cells transplanted into the striatum migrated ventrally and posteriorly towards the SNc. These results suggest that the 6-OHDA damaged brain area attracts grafted NSCs, which migrated from the striatum and survived for a long time in SNc, resulting in behavioral improvement of PD rats.