Schweitzer L, Bell J M, Slotkin T A
Department of Anatomy, Duke University Medical Center, Durham, NC 27710.
Neuroscience. 1987 Dec;23(3):1123-32. doi: 10.1016/0306-4522(87)90186-2.
The dorsal cochlear nucleus is a highly organized nucleus in the auditory system in which the ramifications of depletion of specific cell types during development can be studied. Granule cells, small interneurons that are located in all layers of the DCN in the adult hamster, proliferate postnatally and are, therefore, potentially vulnerable to anti-mitotic agents that are administered after birth. The present experiments describe the effects of alpha-difluoromethylornithine, a drug that inhibits proliferation of cerebellar granule cells, on the granule cells in the dorsal cochlear nucleus. As in the cerebellum, the density of granule cells in the dorsal cochlear nucleus is reduced after alpha-difluoromethylornithine treatment. In hamsters treated with alpha-difluoromethylornithine (200 or 500 mg/kg subcutaneously (s.c.), twice daily on postnatal days 4-14), the numerical density of granule cells was reduced in the superficial dorsal cochlear nucleus at 15 days; by 40 days this effect was also apparent in the deep layer, suggesting that cells located superficially that would have migrated into the deep dorsal cochlear nucleus had either failed to develop or did not arrive at their final location. This evidence suggests that the cells normally migrate down from the superficial proliferative zone into the deeper layers. In the drug-treated animals, a layer of mixed granule cells and fusiform cells was thinner than in controls probably due to the reduction in interspersed granule cells since the number of fusiform cells was unaffected. There was also a dose-dependent effect on cell growth; fusiform cells were affected at both doses, while giant cells were only affected at the highest dose. Granule cells form a major input to the fusiform cells and their depletion may account for some of the effects on fusiform cell growth. There could also be additional direct actions of alpha-difluoromethylornithine on this population.
背侧耳蜗核是听觉系统中一个高度有序的核团，在其中可以研究发育过程中特定细胞类型缺失的影响。颗粒细胞是成年仓鼠背侧耳蜗核各层均有的小型中间神经元，在出生后增殖，因此可能易受出生后给予的抗有丝分裂剂的影响。本实验描述了抑制小脑颗粒细胞增殖的药物α-二氟甲基鸟氨酸对背侧耳蜗核颗粒细胞的影响。与小脑一样，α-二氟甲基鸟氨酸处理后背侧耳蜗核中颗粒细胞的密度降低。在用α-二氟甲基鸟氨酸（200或500mg/kg皮下注射，出生后第4 - 14天每天两次）处理的仓鼠中，15天时浅层背侧耳蜗核中颗粒细胞的数量密度降低；到40天时，这种效应在深层也很明显，这表明原本会迁移到深层背侧耳蜗核的浅层细胞要么未能发育，要么未到达其最终位置。这一证据表明，细胞通常从小层增殖区向下迁移到更深层。在药物处理的动物中，一层混合的颗粒细胞和梭形细胞层比对照组薄，这可能是由于散在的颗粒细胞减少，因为梭形细胞的数量未受影响。对细胞生长也有剂量依赖性效应；两种剂量下梭形细胞均受影响，而巨细胞仅在最高剂量下受影响。颗粒细胞是梭形细胞的主要输入源，它们的减少可能是对梭形细胞生长产生某些影响的原因。α-二氟甲基鸟氨酸对这一细胞群体也可能有额外的直接作用。
