Characterization of heterotopic cell clusters in the hippocampus of the rat after prenatal treatment of methylazoxymethanol acetate.

Prenatal exposure of methylazoxymethanol acetate, a DNA methylating agent, to pregnant rats on embryonic day 15 is known to produce hippocampal malformation and laminar disorganization of the cerebral cortex. However, there are few studies to demonstrate developmental processes of abnormal structures in the hippocampus. In the present study, we examined complete serial sections of rat brains on postnatal day 0 to 2, which pretreated with methylazoxymethanol acetate on embryonic day 15. At birth, massive cellular clusters were found under the white matter of the cerebral cortex and then, a part of these clusters entered into the hippocampal CA1 sector on postnatal day 2. These ectopic cellular clusters in the CA1 were immunoreactive to anti-calbindin antibody, suggesting that the origin of these cellular clusters is equivalent to that of the cortical layer II/III neurons. Next, we injected FluoroGold into the lateral septal nucleus to examine hippocampo-septal projection. FluoroGold-labeled neurons were scattered in the ectopic cellular cluster, implying that CA1 pyramidal neurons project normally to the lateral septal nucleus. In conclusion, a majority of neurons found in the ectopic cellular cluster caused by prenatal methylazoxymethanol treatment is derived from cortical neurons, and some intrinsic pyramidal neurons in the CA1 of hippocampus are scattered throughout the ectopic cellular cluster.