title: Neurogenesis in cerebral heterotopia induced in rats by prenatal methylazoxymethanol treatment.
abstract: We have previously demonstrated that the antiproliferative agent methylazoxymethanol acetate (MAM) is able to induce in rats cerebral heterotopia that share striking similarities with those observed in human periventricular nodular heterotopia (PNH), a cerebral dysgenesis frequently observed in human patients affected by drug-resistant focal epilepsy. In this study, we investigated the time-course of neurogenesis in the cerebral heterotopia of MAM-treated rats, with the idea of understanding why PNH develop in human patients. For these goals, we analyzed the cytoarchitectural features, the time of neurogenesis and the cellular phenotype of the heterotopia, by means of BrdU immunocytochemistry and confocal immunofluorescence experiments. Our data demonstrate that the different types of heterotopia in MAM-treated rats are formed through the same altered neurogenetic process, which follows quite organized neurogenetic gradients. The MAM-induced ablation of an early wave of cortical neurons is sufficient to alter per se the migration and differentiation of subsequently generated neurons, which in turn set the base for the formation of the different heterotopic structures. The neurogenesis of MAM-induced heterotopia may explain the origin and intrinsic epileptogenicity of periventricular nodular heterotopia in human patients.
authors.affiliation: Molecular Neuroanatomy Laboratory, Experimental Neurophysiology Department, Neurological Institute C. Besta, via Celoria 11, 20133 Milan, Italy. battaglia@istituto-besta.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.forename: Silvia
authors.initials: S
authors.lastname: Pagliardini
authors.forename: Laura
authors.initials: L
authors.lastname: Saglietti
authors.forename: Flaminio
authors.initials: F
authors.lastname: Cattabeni
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Stefania
authors.initials: S
authors.lastname: Bassanini
authors.forename: Veronica
authors.initials: V
authors.lastname: Setola
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000196:embryology* / Q000235:genetics / Q000473:pathology*; D001973:Bromodeoxyuridine; D002540:Cerebral Cortex; D002828:Choristoma / Q000139:chemically induced / Q000196:embryology* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives*; D018613:Microscopy, Confocal; D009024:Morphogenesis; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010641:Phenotype; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008746:Methylazoxymethanol Acetate; D001973:Bromodeoxyuridine; C030667:methylazoxymethanol