Expression of calbindin D-28k and parvalbumin in cerebral cortical dysgenesis induced by administration of ethylnitrosourea to rats at the stage of neurogenesis

It has been reported that transplacental administration of ethylnitrosourea (ENU), which is cytotoxic immediately after administration, to rat fetuses at the neurogenesis stage induces dysgenesis of the cerebral cortex, chara cterized by neuronal sparseness and architectural irregularity. In the pres ent study, we examined the topographic distribution of neurons containing 5 -bromo-2-deoxyuridine (BrdU), and those containing calbindin D-28k (CaBP) a nd parvalbumin (PV), most of latter two are considered to be interneurons l ocated in particular layers of the normal cerebral cortex in rats with expe rimentally induced cerebral cortical dysgenesis. Pregnant Wistar albino rat s were given a single transplacental administration of ENU on embryonic day 16, followed 4, 8, 16, 24, 36, or 48 h later by a single intraperitoneal i njection of BrdU. The pups were killed 10 weeks after birth. In the normal cerebral cortex, BrdU-immunopositive neurons showed an inside-out pattern a ccording to the time of BrdU injection, whereas in ENU-treated rats the top ographic localization of the BrdU-immunopositive neurons was irregular and the inside-out pattern was disrupted. Although the number of CaBP- and PV-i mmunopositive neurons was lower in ENU-treated animals, no topographic diff erence was evident between the normal and the dysgenetic cerebral cortices. These findings indicate that the expression of CaBP and PV in the neurons of the rat cerebral cortex is extrinsic, and depends on the position of the neurons rather than on the time of their formation or on genetic control. This suggests the existence of re-regulation of the expression of CaBP and PV in the developing brain, which may be one of the effective mechanisms by which the cerebral cortex can maintain its normal function in spite of cyt oarchitectural abnormality.