Ashwell K W, Webster W S
Department of Anatomy, University of Sydney, N.S.W., Australia.
Neurotoxicol Teratol. 1988 Jan-Feb;10(1):65-73. doi: 10.1016/0892-0362(88)90068-2.
Prenatal exposure of rats to the alkylating agent methylazoxymethanol acetate (MAM Ac) induces severe micrencephaly in the offspring. The aim of the present study was to examine the contribution of primary cell death (due to a direct action of MAM Ac on the neuroepithelium), and secondary (target-dependent) cell death to the subsequent cell deficits in the visual system following prenatal exposure to MAM Ac on embryonic day 11, 12, 13, 14, 15 or 16. The results showed that when primary cell death substantially reduced the neuronal population of a target structure then there was increased target-dependent cell death in the neurons which normally project to that target. This was particularly evident in the dorsal lateral geniculate nucleus following exposure to MAM Ac on E15. Although the MAM Ac caused virtually no primary cell death in the embryonic precursor cells of the dLGN, the nucleus in the adult offspring was reduced by 87% compared with controls. This reduction was shown to be due to increased postnatal target-dependent, or secondary, cell death due to a severe reduction in layers III and IV of the occipital cortex. The cortical damage was due to primary cell death. Hence, primary cell death only partly accounts for the degree of micrencephaly seen in the offspring, consideration of secondary cell death is necessary to understand the total deficit.
大鼠在产前接触烷基化剂乙酸甲基偶氮甲醇（MAM Ac）会导致其后代出现严重的小脑畸形。本研究的目的是探究原发性细胞死亡（由于MAM Ac对神经上皮的直接作用）以及继发性（靶标依赖性）细胞死亡对产前在胚胎第11、12、13、14、15或16天接触MAM Ac后视觉系统中后续细胞缺陷的影响。结果表明，当原发性细胞死亡显著减少靶标结构的神经元数量时，正常投射到该靶标的神经元中靶标依赖性细胞死亡会增加。这在E15接触MAM Ac后的背侧外侧膝状核中尤为明显。尽管MAM Ac在背侧外侧膝状核的胚胎前体细胞中几乎未引起原发性细胞死亡，但成年后代的该核与对照组相比减少了87%。这种减少被证明是由于枕叶皮质III层和IV层严重减少导致出生后靶标依赖性或继发性细胞死亡增加所致。皮质损伤是由原发性细胞死亡引起的。因此，原发性细胞死亡仅部分解释了后代中所见的小脑畸形程度，考虑继发性细胞死亡对于理解总的细胞缺陷是必要的。
