In vitro evidence that the reduction in mesencephalic dopaminergic neurons in the weaver heterozygote is not due to a failure in target cell interaction.
In vitro evidence that the reduction in mesencephalic dopaminergic neurons in the weaver heterozygote is not due to a failure in target cell interaction.
复制标题
体外证据表明，编织者杂合子中脑多巴胺能神经元的减少并不是由于靶细胞相互作用的失败。
DOI：
10.1007/pl00005679
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发表时间：
1997
影响因子：
2
通讯作者：
Heller,A
中科院分区：
文献类型：
--
作者：
Won,L;Ghetti,B;Heller,B;Heller,A
The murineweaver(wv) mutation is characterized by a genetically determined loss of several neuronal populations, which include the nigrostriatal dopaminergic neurons. Animals homozygous for thewvgene exhibit marked deficits in dopaminergic morphological and neurochemical parameters. Thewvgene shows incomplete dominance in that heterozygous (wv/+) mice exhibit moderate reductions in midbrain dopaminergic neuron number. It is unclear whether the dopaminergic neuronal loss in homozygous and heterozygous animals results from an effect of thewvgene solely on the dopaminergic neurons or is due to a failure of interaction of dopaminergic neurons with target cells of the striatum. This issue has been addressed utilizing three-dimensional reaggregate tissue cultures to determine whether thewvgene acts directly on the mesencephalic dopaminergic neurons. Embryonic mesencephalon and striatum fromwv/+ and wild-type (+/+) brains were dissociated and the cells recombined into four mesencephalic-striatal aggregate combinations: (1) mesencephalic(+/+)-striatal(+/+)aggregates; (2) mesencephalic(wv/+)-striatal(wv/+)aggregates; (3) mesencephalic(wv/+)-striatal(+/+)aggregates; and (4) mesencephalic(+/+)-striatal(wv/+)aggregates. At 29 days and 57 days of culture, the number of dopaminergic neurons and dopamine content from mesencephalic-striatal aggregates consisting of mixed genotype or from onlywv/+ tissue were quantitated and compared with that from mesencephalic-striatal cultures prepared from +/+ tissue alone. At both culture time points, aggregates containingwv/+ mesencephalon coaggregated with eitherwv/+ or +/+ striatum contained fewer dopaminergic neurons than mesencephalic-striatal cultures composed of only +/+ cells. Coaggregation of +/+ mesencephalon withwv/+ striatum did not have a detrimental effect on dopaminergic cell number. The findings demonstrate that the difference in the number of mesencephalic dopaminergic neurons betweenwv/+ and +/+ animals seen in vivo can be reproduced in three-dimensional reaggregate culture. Since the coculture of +/+ striatum withwv/+ mesencephalon did not appear to rescuewv/+ dopaminergic neurons in the aggregates as compared towv/+ striatum and,wv/+ striatum proved to be a perfectly adequate target for +/+ mesencephalic dopaminergic neurons, it appears that the effect of thewvgene is on the dopaminergic neurons themselves.
