Neuronal migration disturbance and consequent cytoarchitecture in the cerebral cortex following transplacental administration of methylmercury.
To understand the effects of methylmercury (MeHg) on neuronal migration in the developing cerebral cortex, we performed double administrations of MeHg and 5-bromo-2-deoxyuridine (BrdU) to pregnant rats on different embryonic days (E11, E13, E16 or E21). Histopathological examination of a proportion of the offspring on postnatal day 28 revealed no apparent cytoarchitectural abnormalities in the primary motor and primary somatosensory cortices of the cerebrum. Morphometric analysis revealed no significant differences in total neuron population in either of these areas, and no differences in subpopulations of cells in any of the cortical layers, between any of the MeHg-exposed groups and the control animals. However, BrdU immunohistochemistry revealed an abnormally widespread distribution of the labeled cells throughout cortical layers II-VI of offspring exposed to MeHg on E16 and E21, indicating disruption of the inside-out pattern of neuronal migration. We examined one aspect of cell-fate determination by applying immunohistochemistry with antibodies against calbindin, parvalbumin, calretinin, and gamma-aminobutyric acid, but found no differences in the topographic distributions of the antibody-labeled cells in the cortex between the controls and the MeHg-exposed offspring. These results suggest that it is the extrinsic circumstances - rather than the timing of neuron generation - that regulates the expression of these proteins.
The Brain Disease Research Center, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951-8585, Japan. kakita@bri.niigata-u.ac.jp
Akiyoshi
A
Kakita
Chikanori
C
Inenaga
Mineshi
M
Sakamoto
Hitoshi
H
Takahashi
D000818:Animals; D001973:Bromodeoxyuridine; D064032:Calbindin 2; D064026:Calbindins; D002465:Cell Movement / Q000187:drug effects*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000196:embryology; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008431:Maternal-Fetal Exchange; D008628:Mercury / Q000737:chemistry; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010320:Parvalbumins / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D005680:gamma-Aminobutyric Acid
C576512:Calb2 protein, rat; D064032:Calbindin 2; D064026:Calbindins; D008767:Methylmercury Compounds; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D008628:Mercury; D001973:Bromodeoxyuridine; C004925:methylmercuric chloride