Morphological Changes in the Striatum after Dopaminergic Cell Transplantation to Parkinson's Disease Rat Model / 대한해부학회지

ABSTRACT

Parkinson's disease animal model was developed by the destruction of the striatonigral dopaminergic system. The morphological changes in the dopamine depleted striatum after the transplantation of the fetal mesencephalic dopaminergic neurons or tyrosine hydroxylase cDNA transfected human neural stem cells (C4-TH cells) were studied. Male Sprague-Dawley rats, weighting 250~300 gm, were used. To make unilateral lesion of nigrostriatal tract, 6-OHDA (6 microgram/microliter) was injected into the medial forebrain bundle. Two weeks after the lesion surgery, the effect of the 6-OHDA lesion was assessed by monitoring apomorphine (0.5 mg/kg, s.c)-induced turning behavior and confirmed by the lack of TH-immunoreactivity on tissue sections. Either cell suspension from ventral mesencephalic tissue obtained from embryonic day 14 fetus or C4-TH cells was grafted into the rostral striatum. After grafting, rats were tested with apomorphine every 2 weeks for 6 weeks. The grafted rats showing behavioral recovery were sacrificed and analysed by TH, neuropeptide Y (NPY), and parvalbumin (PV) immuno- histochemistry. TH-immunoreactive (ir) neurons were located around the graft and their processes extended into the striatum. The TH-ir axon terminals made a symmetrical synapse with the dendrites of the striatal neuron. Cell bodies either NPY- or PV-ir striatal neuron were observed around the graft and extended their processes into the graft. TH-ir C4-TH cells were also distributed along the needle track such as the transplanted fetal dopaminergic neurons, but had smaller soma and fewer processes than those. It is concluded that the grafted dopaminergic cells are survived in the dopamine depleted striatum and recovered the rotational behavior of Parkinson's disease animal model.