Li Hong-Peng, Honma Shizuka, Miki Takanori, Takeuchi Yoshiki, Takeuchi Kosei, Kawano Hitoshi
Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, 183-8526, Japan.
Eur J Neurosci. 2005 Apr;21(7):1847-58. doi: 10.1111/j.1460-9568.2005.04018.x.
Prenatal X-ray irradiation is known to result in severe defects of neuronal migration and laminar formation in the cerebral cortex. We examined the formation of cortical afferent and efferent pathways in rats that had been exposed to X-ray irradiation (1.0 Gy) at embryonic day 14 (E14), by birthdating with bromodeoxyuridine (BrdU) and axonal labeling with 1-1'-dioctodecyl-3,3,3',3'- tetramethyl-indocarbocyanine perchlorate (DiI), in addition to immunohistochemical staining for various axonal markers including neurofilament, and cell adhesion molecules L1 and TAG-1. The results obtained were as follows. (i) The neuroepithelium formed germinal rosettes and concavities in the cortical anlage from 2 days after irradiation. Neurons generated in the neuroepithelium accumulated to form subcortical heterotopia and obstructed pathway formation in the intermediate zone, resulting in an aberrant trajectory of TAG-1-immunoreactive cortical efferent axons. (ii) In rats exposed to X-ray irradiation at E14, cystic cavities were formed in the cortex-striatum boundary region between E15 and E17, probably because of delayed cell death of neurons generated at E14. These cavities transiently interrupted both cortical afferent (L1-positive) and efferent (TAG-1-positive) axons. (iii) X-ray irradiation at E14 partially destroyed subplate neurons (transient targets of thalamic afferent axons) and disturbed the arrangement of the subplate layer. This resulted in a misrouting of neurofilament- and L1-immunoreactive thalamocortical axons that obliquely traversed the cortical plate to run up to the superficial layer. The present study demonstrates for the first time that X-ray irradiation during initial cortical development causes multiple defects in the formation of cortical afferent and efferent pathways.
已知产前X射线照射会导致大脑皮质神经元迁移和层状结构形成出现严重缺陷。我们通过用溴脱氧尿苷（BrdU）进行出生时间标记、用1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐（DiI）进行轴突标记，以及对包括神经丝、细胞黏附分子L1和TAG-1在内的各种轴突标记物进行免疫组织化学染色，研究了在胚胎第14天（E14）接受X射线照射（1.0 Gy）的大鼠皮质传入和传出通路的形成。得到的结果如下。（i）照射后2天，神经上皮在皮质原基中形成生发玫瑰花结和凹陷。在神经上皮中产生的神经元聚集形成皮质下异位，阻碍了中间带的通路形成，导致TAG-1免疫反应性皮质传出轴突的轨迹异常。（ii）在E14接受X射线照射的大鼠中，E15至E17期间在皮质-纹状体边界区域形成了囊腔，这可能是由于E14产生的神经元细胞死亡延迟所致。这些囊腔暂时中断了皮质传入（L1阳性）和传出（TAG-1阳性）轴突。（iii）E14的X射线照射部分破坏了板下神经元（丘脑传入轴突的临时靶点），扰乱了板下层的排列。这导致神经丝和L1免疫反应性丘脑皮质轴突错误布线，这些轴突斜穿皮质板向上延伸至表层。本研究首次证明，在皮质发育初期进行X射线照射会导致皮质传入和传出通路形成出现多种缺陷。
