Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury.
Transplacental administration of methylmercury (MeHg) induces disruption of neuronal migration in the developing cerebral cortex. However, the effects of MeHg on glial progenitor migration remain unclear. To understand this, we performed double administration of MeHg and 5-bromo-2-deoxyuridine (BrdU) to neonatal rat pups on postnatal day 2 (P2), when glial cells are generated from progenitors in the subventricular zone (SVZ). Histopathological examination of a proportion of the MeHg-treated rats on P28 revealed no apparent abnormalities of cytoarchitecture or neuron count in either the primary motor or primary somatosensory cortex of the cerebrum. BrdU immunohistochemistry revealed abnormal accumulation of the labeled cells in the deeper layers of the cortices and underlying white matter of both areas, where an excessive number of astrocytes (glial fibrillary acidic protein- or S-100beta-immunolabeled cells) and oligodendrocytes (2',3'-cyclic-nucleotide 3'-phosphohydrolase-labeled cells) were located. Next, to investigate the migration of individual progenitors from the forebrain SVZ of P2 neonates, we labeled them in vivo with a retrovirus encoding green fluorescent protein (GFP), following administration of MeHg, and then examined the distribution pattern of the GFP-labeled cells in the P28 cerebrum. We found that the labeled cells developed into astrocytes and oligodendrocytes and were accumulated abnormally in the lateral white matter as well as in the adjacent deeper layer of the lateral cortex and lateral side of the striatum. Thus, exposure to MeHg in the gliogenic period induced irregular distribution of glia as a consequence of abnormal migration of the postnatal progenitors.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000187:drug effects*; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D008767:Methylmercury Compounds / Q000633:toxicity*; D009414:Nerve Growth Factors / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013687:Telencephalon / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D014018:Tissue Distribution
D005904:Glial Fibrillary Acidic Protein; D008767:Methylmercury Compounds; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D001973:Bromodeoxyuridine; C004925:methylmercuric chloride