Neuronal apoptosis and gray matter heterotopia in microcephaly produced by cytosine arabinoside in mice

Brain Research
Tomoyuki TakanoMasaki Ohno

Abstract

Primary microcephaly can be accompanied by numerous migration anomalies. This experiment was undertaken to examine the pathogenesis of gray matter heterotopia and microcephaly that is produced after administering cytosine arabinoside (Ara-C) to mice. Pregnant mice were intraperitoneally injected with Ara-C at 30 mg/kg body weight on days 13.5 and 14.5 of gestation, and then their offspring were examined. On embryonic day 15.5, in the ventricular zone of the cingulate cortex, the neuroepithelial cells lacked BrdU immunoreactivity. Nestin-immunoreactive radial glial fibers and calretinin-positive subplate fibers were disrupted. TUNEL reaction was remarkable throughout the cerebral hemisphere. Subcortical heterotopia in the cingulate cortex and subependymal nodular heterotopia in the dorsolateral part of the lateral ventricles became detectable by the first day after birth. Thirty-two days after birth, microcephaly was apparent; subcortical heterotopia was observed to have increased in size while it was still located in the frontal and cingulate cortices. This experiment demonstrated that Ara-C induces neuronal apoptosis throughout the cerebral hemisphere. The immunohistochemical characteristics in the gray matter heterotopia sugg...Continue Reading

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Citations

Nov 26, 2009·Brain : a Journal of Neurology·A James BarkovichWilliam B Dobyns
Jul 9, 2011·The Journal of Clinical Investigation·Sandrine PassemardVincent Lelièvre
Nov 10, 2013·The Journal of Veterinary Medical Science·Jing SunSatoshi Furukawa
Mar 15, 2011·The European Journal of Neuroscience·Antoine Nissant, Marta Pallotto
May 9, 2012·European Journal of Medical Genetics·Marije E C Meuwissen, Grazia M S Mancini

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis