PubMed · 11655592
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Donald DeMarco. 1983. On human experimentation.. https://pubmed.ncbi.nlm.nih.gov/11655592/
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Mutated doublecortin (DCX) gives rise to severe abnormalities in human cortical development. Adult Dcx knockout mice show no major neocortical defects but do have a disorganized hippocampus. We report here the developmental basis of these hippocampal abnormalities. A heterotopic band of neurons was identified starting at E17.5 in the CA3 region and progressing throughout the CA1 region by E18.5. At neonatal stages, the CA1 heterotopic band was reduced, but the CA3 band remained unchanged, continuing into adulthood. Thus, in mouse, migration of CA3 neurons is arrested during development, whereas CA1 cell migration is retarded. On the Sv129Pas background, magnetic resonance imaging (MRI) also suggested abnormal dorsal hippocampal morphology, displaced laterally and sometimes rostrally and associated with medial brain structure abnormalities. MRI and cryosectioning showed agenesis of the corpus callosum in Dcx knockout mice on this background and an intermediate, partial agenesis in heterozygote mice. Wild-type littermates showed no callosal abnormalities. Hippocampal and corpus callosal abnormalities were also characterized in DCX-mutated human patients. Severe hippocampal hypoplasia was identified along with variable corpus callosal defects ranging from total agenesis to an abnormally thick or thin callosum. Our data in the mouse, identifying roles for Dcx in hippocampal and corpus callosal development, might suggest intrinsic roles for human DCX in the development of these structures.
Nestin is considered a marker of neurogenic and myogenic precursor cells. Its arrangement is regulated by cyclin-dependent kinase 5 (CDK5), which is expressed in murine podocytes. We investigated nestin expression in human adult and fetal kidney as well as CDK5 presence in adult human podocytes. Confocal microscopy demonstrated that adult glomeruli display nestin immunoreactivity in vimentin-expressing cells with the podocyte morphology and not in cells bearing the endothelial marker CD31. Glomerular nestin-positive cells were CDK5 immunoreactive as well. Western blotting of the intermediate filament-enriched cytoskeletal fraction and coimmunoprecipitation of nestin with anti-CDK5 antibodies confirmed these results. Nestin was also detected in developing glomeruli within immature podocytes and a few other cells. Confocal microscopy of experiments conducted with antibodies against nestin and endothelial markers demonstrated that endothelial cells belonging to capillaries invading the lower cleft of S-shaped bodies and the immature glomeruli were nestin immunoreactive. Similar experiments carried out with antibodies raised against nestin and alpha-smooth muscle actin showed that the first mesangial cells that populate the developing glomeruli expressed nestin. In conclusion, nestin is expressed in the human kidney from the first steps of glomerulogenesis within podocytes, mesangial, and endothelial cells. This expression, restricted to podocytes in mature glomeruli, appears associated with CDK5.
Neospora caninum is an apicomplexan protozoan which causes abortion in cattle worldwide. The present study was designed to assess the importance of bovine neosporosis for causing abortion in Iranian cattle. Infection was primarily diagnosed by polymerase chain reaction (PCR), complemented with histopathology and immunohistochemistry (IHC). One hundred brains of aborted bovine fetuses were collected from Iranian dairy herd between 2003 and 2005 in Mashhad area. N. caninum was detected by PCR in the brains of 13 aborted fetuses. Lesions consistent with N. caninum infection were observed in 12 of fetal brains. Immunohistochemical examination of brain detected N. caninum organisms in three aborted fetuses, and a thick-walled (2 mum) cyst with 50 mum diameter was identified in one of the IHC-positive brain. The results indicated that neosporosis is an important cause of abortion in dairy cattle of Iran.