Funahashi A, Inouye M, Yamamura H
Research Institute of Environmental Medicine, Nagoya University, Japan.
Acta Neuropathol. 1992;85(1):31-8. doi: 10.1007/BF00304631.
Prenatal exposure of pregnant rats to methylazoxymethanol acetate (MAM), an anti-mitotic agent, on day 15 of gestation induces severe microcephaly in the offspring. The present study first investigated a developmental alteration of serotonin (5HT) neurons immunohistochemically in the dorsal and median raphe nuclei in serial sections in both control and microcephalic rats (MAM-rats) at 35 days of age. 5HT-immunoreactive neurons in the MAM-rats were reduced in number and irregularly distributed in the dorsal and median raphe nuclei compared with those in the control. The dendrites of neurons in these nuclei in the MAM-rats were very short and twisted. A follow-up observation on the development of the cerebral cortex at 5, 9 and 28 days of age was performed using Nissl-stained preparations, which revealed a disorganized cell arrangement in the cerebral cortex of the MAM-rats at the very early postnatal period. Furthermore, the distribution of 5HT-immunoreactive fibers into the cerebral cortex was also examined using brains of 28 days of age. In MAM-rats of this age, abnormally tortuous 5HT-immunoreactive fibers were observed in the cerebral cortex. 5HT neurons in the raphe nuclei are known to project their ascending axons widely into the entire cortical area during the 1st postnatal week. Thus, the association of disorganized cortical cell arrangement and the hyperdense and tortuous distribution of 5HT-immunoreactive fibers in the cerebral cortex support the idea of target-dependent secondary degeneration of 5HT neurons in the dorsal and median raphe nuclei of the MAM-rats.
在妊娠第15天给怀孕大鼠产前暴露于抗有丝分裂剂乙酸甲基偶氮甲醇（MAM），会导致后代出现严重小头畸形。本研究首先在35日龄的对照大鼠和小头畸形大鼠（MAM大鼠）的连续切片中，通过免疫组织化学方法研究了中缝背核和中缝正中核中5-羟色胺（5HT）神经元的发育变化。与对照组相比，MAM大鼠中5HT免疫反应性神经元数量减少，在中缝背核和中缝正中核中分布不规则。MAM大鼠这些核中的神经元树突非常短且扭曲。使用尼氏染色制剂对5日龄、9日龄和28日龄的大脑皮质发育进行了随访观察，结果显示在出生后早期，MAM大鼠的大脑皮质细胞排列紊乱。此外，还使用28日龄大鼠的大脑检查了5HT免疫反应性纤维向大脑皮质的分布情况。在这个年龄段的MAM大鼠中，在大脑皮质中观察到异常扭曲的5HT免疫反应性纤维。已知中缝核中的5HT神经元在出生后第一周将其上升轴突广泛投射到整个皮质区域。因此，大脑皮质中细胞排列紊乱与5HT免疫反应性纤维高密度和扭曲分布之间的关联支持了MAM大鼠中缝背核和中缝正中核中5HT神经元发生靶依赖性继发性变性的观点。
