Ashwell K
Department of Anatomy, University of Sydney, N.S.W., Australia.
Exp Brain Res. 1987;68(2):329-38. doi: 10.1007/BF00248799.
The morphology of neurons in the dorsal lateral geniculate nucleus (dLGN) of rats made micrencephalic by prenatal exposure (E13 or E15) to the cytotoxic agent, methylazoxymethanol acetate, has been examined in Golgi impregnations. Type B neurons were unaffected by exposure on either day while type A neurons showed significant reductions in both soma diameter and dendritic field area following exposure on E15, but not E13. These results indicate that target deprivation of type A neurons (by destruction of neurons in the granular and supragranular layers of the occipital cortex with exposure on E15) has a more significant effect on development of type A neurons than the direct cytotoxic action of the agent on precursors of dorsal lateral geniculate nucleus neurons in the fetal thalamus (seen with exposure on E13 in a previous study). The findings are significant because they indicate that the indirect effects of cytotoxic teratogens on the developing brain (acting via the target dependence of some neuronal classes) may cause structural und functional alterations in the brain which differ from those predicted on the basis of the direct action above. This study also shows that the percentage of relay neurons in the dorsal lateral geniculate nucleus is unaffected in animals exposed to the agent on E15, despite pronounced reductions in neuronal numbers and changes in relay neuron morphology.
通过高尔基染色法,研究了产前暴露于细胞毒性剂乙酸甲基偶氮甲醇(分别在胚胎期第13天或第15天)的微小脑大鼠背外侧膝状核(dLGN)中神经元的形态。B型神经元在这两天的暴露下均未受影响,而在胚胎期第15天暴露后,A型神经元的胞体直径和树突野面积均显著减小,但在胚胎期第13天暴露后则未出现这种情况。这些结果表明,A型神经元的靶剥夺(胚胎期第15天暴露导致枕叶皮质颗粒层和颗粒上层神经元被破坏)对A型神经元发育的影响,比该药剂对胎儿丘脑背外侧膝状核神经元前体的直接细胞毒性作用(在之前的一项研究中观察到胚胎期第13天暴露的情况)更为显著。这些发现意义重大,因为它们表明细胞毒性致畸剂对发育中大脑的间接影响(通过某些神经元类别的靶依赖性起作用)可能导致大脑结构和功能的改变,这些改变与基于上述直接作用所预测的情况不同。本研究还表明,尽管神经元数量显著减少且中继神经元形态发生变化,但在胚胎期第15天暴露于该药剂的动物中,背外侧膝状核中继神经元的百分比并未受到影响。