Micro-transplantation of ganglionic eminence cells reduces Huntington-associated phenotypes in rats

Abstract

Objective To compare the therapeutic effects of microtransplantation method and traditional transplantation method for transplanting ganglionic eminence cell into HD rats. Methods Seventy-five adult female Sprague-Dawley rats were randomly divided into four groups, control group (ctrl; n=15), sham transplantation group (ST; n=20), traditional transplantation group (TT; n=20), and microtransplantation group (MT; n=20). Ganglionic eminence cells or phosphate-buffered saline were transplanted into unilateral striatum of quinic acid lesion rats with micro-transplantation instruments (with an outer diameter of 50 μm) or traditional transplantation instruments (with an outer diameter of 470 μm). Apomorphine-induced rotation test and adjusting step test were assessed after QA-induced lesion and 2, 4, 6, 8, 10 and 12 weeks after transplantation. The expression of neuronal nuclei (NeuN), dopamine, cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), and glial fibrillary acidic protein (GFAP) were analyzed at 12 weeks after transplantation. Results Compared with traditional transplantation group, microtransplantation group performed well in stepping test. DARPP-32 positives cell in MT group(13 194±976) had a significantly larger number compared with TT group(9 690±651) (P=0.020). The TT group(11 352± 1 421) had a significantly larger number of GFAP-positive cells compared with MT groups (6 558±694)(P=0.002). The survival rate of the MT group(85%) during the 12 weeks after transplantation was significantly higher than that of the TT groups(55%)(P=0.012). Conclusion Micro-transplantation approach can minimize the trauma associated with transplantation and also provide accurate targets in the host brain. It may be an alternative transplantation strategy for Huntington's disease. Key words: Ganglionic eminence cell; Micro-transplantation; Rat model of Huntington's disease; Cell survival; Functional recovery