Cerebral cortex of the mouse after prenatal chemical insult.

Abstract

AbstractThe purpose of this study was to examine whether a short term chemical insult to neuroepithelial cells (the matrix cells of neurons) causes a clearly defined neuronal deficit in the neocortex and hippocampal region. In the first experiment 15‐day pregnant mice were given a single dose of 5‐azacytidine (4 mg/kg); 30–60 minutes later they were injected with tritiated thymidine (6 μc/g). The fetuses were sacrificed at various hours and days after treatment. No cellular abnormalities were observed one or two hours after treatment with 5‐azacytidine, but at three to four hours abnormal mitotic figures became visible at the lumen. Usually the chromosomes were clumped together, forming commaand circle‐shaped structures. Sometimes chromosome breaks were observed. The number of cells with chromosomal abnormalities increased during the following hours, but ten hours after treatment a few normal mitotic figures appeared again. In the meantime the affected cells moved from the lumen toward the cortical plate. Their number gradually decreased and 48 hours after treatment all had disappeared. Since in the controls many labeled cells reached the cortex but in the experimental animals none, a neuronal deficit resulted from the treatment. It was difficult, however, to pinpoint the type of neuron lacking in the brain of the treated newborn. In the second experiment pregnant animals were given several doses of 5‐azacytidine (2 mg/kg on days 13, 14 and 15 of gestation) and sacrificed at various days after birth. The neocortex as well as the hippocampal region of the treated animals contained fewer cells than the same structures in the controls. In addition many neurons both in the cortex and hippocampus were morphologically abnormal. It is thus concluded that single and repeated shortterm chemical insults to neuroepithelial cells during the later stages of fetal life, result in a shortage of neurons and the presence of morphologically abnormal neurons.