Different patterns of abnormal neuronal migration in the cerebral cortex of mice prenatally exposed to irradiation.

A characteristic abnormal cortical architecture in the adult brain was produced in mice subjected to 1.5 Gy of X-irradiation on embryonic day 14. Neurons in the lateral regions were organized into an essentially six-layered structure, while neurons in the dorsal regions formed a unique four-layered cortex. The patterns of neuronal migration in these different cortical regions were examined with immunohistochemistry for anti-bromodeoxyuridine (BrdU), anti-midkine (MK), and anti-glial fibrillary acidic protein (GFAP) antibodies. In the cortical lateral region, BrdU-labeled cells in the upper layers were fewer, and those in lower layers more numerous in prenatally irradiated mice than in control, while in the dorsal region (four-layered region), BrdU-labeled cells were very few in layer 2, and a large number of labeled-cells remained in layer 4. These results indicated that some neuroblasts in the lateral cortical region could not migrate to the upper layers, and that most neuroblasts in the dorsal cortical region failed to pass through the earlier migration zone. MK- and GFAP-stained radial glial fibers showed that the radial fibers were consistently oriented in the direction of neuronal migration in the control brains. However, in the irradiated brain, such radial fibers were crumpled in the lateral region, or were reduced markedly in number in some parts of the dorsal region. These results revealed that neuronal migratory pathways (radial glial fibers) were destroyed differently in different regions, and that X-rays killed some cells including radial glial cells or their precursors during the embryonic stage. These effects of radiation on the developing brain may result from the possibility that neurogenetic time is different or there are cellular mechanisms involved in the radiosensitivity among different regions.