Funahashi A, Fujimiya M, Kimura H, Maeda T
School of Informatics and Sciences, Nagoya University, Japan.
Acta Neuropathol. 1998 Jan;95(1):5-14. doi: 10.1007/s004010050760.
The postnatal development of serotonin (5HT)-immunoreactive axons was studied in the visual cortex of the cerebrum in both normal and microcephalic rats during early postnatal and young adult stages. Severe microcephaly in rat offspring was induced by prenatal exposure to methylazoxymethanol acetate (MAM), an anti-mitotic agent, on day 15 of gestation. From postnatal day 1 (PND 1) to PND 5, fine and short 5HT fibers were irregularly dispersed throughout the occipital cortex in both the control and MAM-treated rats (MAM-rats). A conspicuous aggregation of dot-like 5HT terminals was found in controls, but not in MAM-rats, in a shallow layer of the dorsomedial region of the occipital cortical plate. On PND 7, such an aggregation of 5HT terminals was found in both groups. The density of the aggregation increased up to PND 9, but then decreased gradually, finally becoming unrecognizable at around PND 15 in both groups. MAM-rats, however, always showed hyperaggregation of 5HT terminals when compared with controls on the same PND. The density of 5HT fibers gradually increased, and finally made up a network-like formation at PND 28 in both groups, its pattern was essentially identical to the abnormal distribution of 5HT fibers during the later stage. As a result, the network-like formation of 5HT fibers in the MAM-rats at PND 28 was markedly twisted and somewhat hyperdense. In Nissl-stained preparations from PND 9 to 15, the 5HT terminal aggregation in the control rats was precisely confined to the newly forming layer IV of the visual cortex. In the MAM-rats, on the other hand, the aggregation of 5HT terminals was not associated with a specific cortical layer because of a disarranged cytoarchitecture of the microcephaly.
在出生后早期和年轻成年阶段，对正常和小头畸形大鼠大脑视觉皮层中5-羟色胺（5HT）免疫反应性轴突的产后发育进行了研究。在妊娠第15天，通过产前暴露于抗有丝分裂剂乙酸甲基偶氮甲醇（MAM）诱导大鼠后代出现严重小头畸形。从出生后第1天（PND 1）到PND 5，对照大鼠和MAM处理大鼠（MAM大鼠）的枕叶皮质中均有细小且短的5HT纤维不规则地分散分布。在枕叶皮质板背内侧区域的浅层，对照大鼠中发现了点状5HT终末的明显聚集，而MAM大鼠中未发现。在PND 7时，两组均发现了这种5HT终末的聚集。聚集密度在PND 9时增加，但随后逐渐降低，最终在两组中PND 15左右变得无法辨认。然而，与同一PND的对照相比，MAM大鼠始终表现出5HT终末的过度聚集。5HT纤维的密度逐渐增加，最终在PND 28时在两组中形成网络状结构，其模式与后期5HT纤维的异常分布基本相同。结果，PND 28时MAM大鼠中5HT纤维的网络状结构明显扭曲且密度略高。在PND 9至15的尼氏染色制剂中，对照大鼠中的5HT终末聚集精确地局限于视觉皮层新形成的IV层。另一方面，在MAM大鼠中，由于小头畸形导致细胞结构紊乱，5HT终末的聚集与特定的皮质层无关。
