title: Heterotopia in microcephaly induced by cytosine arabinoside: hippocampus in the neocortex.
abstract: Pregnant mice were injected intraperitoneally with cytosine arabinoside (Ara-C) on days 13.5 and 14.5 of pregnancy. The brains of their offspring were studied histologically and histochemically. In addition to dysgenic microcephaly, nodular structures consisting of cells with a relatively homogeneous morphology were observed in the depths of the cerebral cortex. The cell clusters were first seen around postnatal day 4, and had a cellular continuity with the disarrayed pyramidal cell layer in the CA 1 region of the hippocampus. Golgi-Cox staining showed a number of pyramidal-shaped cells in the clusters. Morphologically, they resembled the pyramidal neurons of the hippocampus. Immunohistochemical examination, using anti-serotonin or anti-tyrosine hydroxylase antibodies, also indicated similarities between the cell clusters and the pyramidal cell layer. It is, therefore, proposed that the cell clusters consisted of heterotopic pyramidal cells of the hippocampus. A few synaptic structures could already be detected in the heterotopic cell clusters on postnatal day 3 by electron microscopy. This early establishment of synaptic contact with related neurons may have caused the heterotopic localization of the pyramidal cells.
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Japan. kumiyo@belle.shiga-med.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Ono-Yagi
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Iwami
authors.forename: T
authors.initials: T
authors.lastname: Takano
authors.forename: T
authors.initials: T
authors.lastname: Yamano
authors.forename: M
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000633:toxicity*; D002828:Choristoma / Q000139:chemically induced*; D003561:Cytarabine / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006624:Hippocampus / Q000196:embryology / Q000473:pathology; D008431:Maternal-Fetal Exchange; D051379:Mice; D008813:Mice, Inbred ICR; D008831:Microcephaly / Q000139:chemically induced* / Q000473:pathology; D009024:Morphogenesis / Q000187:drug effects; D019579:Neocortex / Q000196:embryology / Q000473:pathology*; D009412:Nerve Fibers / Q000737:chemistry / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D012701:Serotonin / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D000963:Antimetabolites; D009419:Nerve Tissue Proteins; D003561:Cytarabine; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase