title: Multiple defects in the formation of rat cortical axonal pathways following prenatal X-ray irradiation.
abstract: 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.
authors.affiliation: Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, 183-8526, Japan.
authors.forename: Hong-Peng
authors.initials: HP
authors.lastname: Li
authors.forename: Shizuka
authors.initials: S
authors.lastname: Honma
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Kosei
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawano
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D064026:Calbindins; D002232:Carbocyanines / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D058969:Contactin 2; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000528:radiation effects; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D037181:Lectins, C-Type; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D058580:Neurocan; D016900:Neurofilament Proteins / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014965:X-Rays / Q000009:adverse effects*
chemical_list: C035005:3,3'-dihexadecylindocarbocyanine; C548674:CNTN2 protein, human; D064026:Calbindins; D002232:Carbocyanines; D015816:Cell Adhesion Molecules, Neuronal; D011508:Chondroitin Sulfate Proteoglycans; C548676:Cntn2 protein, rat; D058969:Contactin 2; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D058580:Neurocan; D016900:Neurofilament Proteins; D018809:Proliferating Cell Nuclear Antigen; D064030:S100 Calcium Binding Protein G; C076817:NCAN protein, human; D001973:Bromodeoxyuridine