title: Developmentally induced microencephalopathy in guinea pigs--embryonic glial cell activation marks selective neuronal death.
abstract: We have recently shown that in utero treatment of guinea pigs with the DNA methylating substance methylazoxymethanol acetate (MAM) on gestation day (GD) 24 results in neocortical microencephalopathy, increased protein kinase C activity and altered processing of the amyloid precursor protein in neocortex of the offsprings. In order to identify the primary neuronal lesions produced by MAM-treatment, we mapped the 5-bromo-2'-deoxyuridine (BrdU)-incorporation in dividing neurons on GD 24 and we followed the effects of MAM-treatment on GD 24 on embryonic immediate early gene expression and on glial cell activation. BrdU injected on GD 24 labeled many neurons of the ventricular zone and of the intermediate zone but only scattered neurons of the cortical plate. When time-mated guinea pigs were injected intraperitoneally with MAM on GD 24, we observed the activation of microglial cells in the ventricular/intermediate zone and the appearence of astrocytes between the intermediate zone and the cortical plate, 48 h after intoxification. The activation of glial cells was accompanied by the neuronal expression of c-Fos but not of c-Jun in the ventricular/intermediate zone. Based on our observations on BrdU-incorporation and on the morphological outcome of MAM treatment in the juvenile guinea pig, our data presented here indicate that selective neurodegeneration during development induces the activation of both phagocytotic microglial cells and of astrocytes which might trophically support damaged neurons surviving this lesion procedure.
authors.affiliation: Department of Neurochemistry, Paul Flechsig Institute for Brain Research, Jahnallee 59, 04109, Leipzig, Germany. ross@medizin.uni-leipzig.de
authors.forename: S
authors.initials: S
authors.lastname: Rossner
authors.forename: M K
authors.initials: MK
authors.lastname: Brückner
authors.forename: V
authors.initials: V
authors.lastname: Bigl
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D001973:Bromodeoxyuridine; D016923:Cell Death / Q000187:drug effects; D005260:Female; D017781:Genes, Immediate-Early / Q000502:physiology; D006168:Guinea Pigs; D008746:Methylazoxymethanol Acetate; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D019579:Neocortex / Q000002:abnormalities* / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D000963:Antimetabolites; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D008746:Methylazoxymethanol Acetate; D011493:Protein Kinase C; D001973:Bromodeoxyuridine