MESENCEPHALIC GRAFTS PARTIALLY RESTORE NORMAL NIGRAL DYNORPHIN LEVELS IN 6-HYDROXYDOPAMINE-LESIONED RATS TREATED CHRONICALLY WITH L-DIHYDROXYPHENYLALANINE

被引:9
作者
ROY, E
COTE, PY
GREGOIRE, L
PARENT, A
BEDARD, PJ
机构
[1] UNIV LAVAL,CTR RECH NEUROBIOL,QUEBEC CITY,PQ G1J 1Z4,CANADA
[2] HOP ENFANTS JESUS,QUEBEC CITY,PQ G1J 1Z4,CANADA
关键词
D O I
10.1016/0306-4522(94)00580-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
An increase of dynorphin levels is commonly observed in the substantia nigra of 6-hydroxydopamine-lesioned rats chronically treated with daily injections of L-DOPA. This study investigates the potential of fetal mesencephalic grafts to restore normal levels of dynorphin in such cases. After 19 consecutive days of treatment with L-DOPA, lesioned rats with the most severe nigral cell loss showed increased levels of dynorphin in the substantia nigra ipsilateral to the lesion, as expected. The changes were assessed by standard immunohistochemical techniques combined with the use of an image analysis system. Such changes were not observed in the substantia nigra of rats that received fetal mesencephalic cells in the striatum six months prior to the beginning of the chronic treatment. However, only animals displaying heavy loss of dopaminergic neurons in the substantia nigra pars compacta showed significant changes of dynorphin levels in the substantia nigra following drug treatment. Our results show that fetal nigral cells transplanted into the striatum have the potential to prevent biochemical changes observed in the basal ganglia induced by the lesion of the nigrostriatal pathway and chronic treatment with L-DOPA. It is still hypothesized from studies in rodents that this peptide may play a role in the appearance of DOPA-induced dyskinesia, because dynorphin levels increase in the substantia nigra pars reticulata after L-DOPA treatment. If this happens to be the case, then the use of fetal nigral grafts could therefore be an important step to prevent the induction of dyskinesia after chronic L-DOPA treatment.
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页码:413 / 425
页数:13
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