Expression of calbindin D-28k and parvalbumin in cerebral cortical dysgenesis induced by administration of ethylnitrosourea to rats at the stage of neurogenesis.
It has been reported that transplacental administration of ethylnitrosourea (ENU), which is cytotoxic immediately after administration, to rat fetuses at the neurogenesis stage induces dysgenesis of the cerebral cortex, characterized by neuronal sparseness and architectural irregularity. In the present study, we examined the topographic distribution of neurons containing 5-bromo-2-deoxyuridine (BrdU), and those containing calbindin D-28k (CaBP) and parvalbumin (PV), most of latter two are considered to be interneurons located in particular layers of the normal cerebral cortex in rats with experimentally induced cerebral cortical dysgenesis. Pregnant Wistar albino rats were given a single transplacental administration of ENU on embryonic day 16, followed 4, 8, 16, 24, 36, or 48 h later by a single intraperitoneal injection of BrdU. The pups were killed 10 weeks after birth. In the normal cerebral cortex, BrdU-immunopositive neurons showed an inside-out pattern according to the time of BrdU injection, whereas in ENU-treated rats the topographic localization of the BrdU-immunopositive neurons was irregular and the inside-out pattern was disrupted. Although the number of CaBP- and PV-immunopositive neurons was lower in ENU-treated animals, no topographic difference was evident between the normal and the dysgenetic cerebral cortices. These findings indicate that the expression of CaBP and PV in the neurons of the rat cerebral cortex is extrinsic, and depends on the position of the neurons rather than on the time of their formation or on genetic control. This suggests the existence of re-regulation of the expression of CaBP and PV in the developing brain, which may be one of the effective mechanisms by which the cerebral cortex can maintain its normal function in spite of cytoarchitectural abnormality.
Oyanagi
K
K
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan. k123ysm@tmin.ac.jp
Kakita
A
A
Kawasaki
K
K
Hayashi
S
S
Yamada
M
M
D000014:Abnormalities, Drug-Induced / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry; D064026:Calbindins; D048429:Cell Size; D004261:DNA Replication / Q000187:drug effects; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D008297:Male; D009024:Morphogenesis / Q000187:drug effects; D019579:Neocortex / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D010320:Parvalbumins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis* / Q000235:genetics
D064026:Calbindins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005038:Ethylnitrosourea