Zeng B Y, Jenner P, Marsden C D
Neurodegenerative Disease Research Centre, Biomedical Sciences Division, King's College, London, U.K.
Mov Disord. 1996 Jan;11(1):43-52. doi: 10.1002/mds.870110109.
In situ hybridization histochemistry was used to investigate the expression of striatal preproenkephalin and preprotachykinin messenger ribonucleic acid (mRNA) in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway followed 4 weeks later by implantation of foetal dopamine cells into the denervated striatum. Striatal dopamine deafferentation caused an (+)-amphetamine-induced rotational asymmetry, an increase in striatal preproenkephalin mRNA message, and a decrease in striatal preprotachykinin mRNA message relative to control animals. Two months after grafting a foetal ventral mesencephalon suspension, there was reversal of the rotational asymmetry to (+)-amphetamine. At this time the increase in striatal preproenkephalin mRNA was significantly attenuated and the decrease in preprotachykinin mRNA was partially reversed compared to animals with a 6-hydroxydopamine lesion alone. Subregional analysis showed the attenuation of the increase in preproenkephalin mRNA to occur in dorsolateral, dorsomedial and ventromedial, but not ventrolateral, striatal subdivisions. The partial reversal of the decreased preprotachykinin mRNA density after grafting was only statistically significant in the DM and VM subdivisions. These results demonstrate graft-induced partial recovery of striatal function, as judged by preproenkephalin and preprotachykinin mRNA levels, within 2 months of transplantation.
采用原位杂交组织化学法,研究黑质纹状体通路经6-羟基多巴胺损伤的大鼠纹状体前脑啡肽原和前速激肽原信使核糖核酸(mRNA)的表达情况。4周后,将胎儿多巴胺细胞植入去神经支配的纹状体。相对于对照动物,纹状体多巴胺去传入导致(+)-苯丙胺诱导的旋转不对称、纹状体前脑啡肽原mRNA信息增加以及纹状体前速激肽原mRNA信息减少。移植胎儿腹侧中脑悬液两个月后,(+)-苯丙胺诱导的旋转不对称发生逆转。此时,与仅接受6-羟基多巴胺损伤的动物相比,纹状体前脑啡肽原mRNA的增加显著减弱,前速激肽原mRNA的减少部分逆转。亚区域分析显示,前脑啡肽原mRNA增加的减弱发生在背外侧、背内侧和腹内侧纹状体亚区,而腹外侧纹状体亚区未出现这种情况。移植后前速激肽原mRNA密度降低的部分逆转仅在背内侧和腹内侧亚区具有统计学意义。这些结果表明,移植后2个月内,以前脑啡肽原和前速激肽原mRNA水平判断,移植可诱导纹状体功能部分恢复。