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Cerebral Cortex, Vol. 12, No. 9, 954-960, September 2002
© 2002 Oxford University Press

Altered Spatial Arrangement of Layer V Pyramidal Cells in the Mouse Brain following Prenatal Low-dose X-Irradiation. A Stereological Study using a Novel Three-dimensional Analysis Method to Estimate the Nearest Neighbor Distance Distributions of Cells in Thick Sections

Christoph Schmitz, Norman Grolms, Patrick R. Hof1, Robert Boehringer2, Jacob Glaser2 and Hubert Korr

Department of Anatomy and Cell Biology, RWTH University of Aachen, Germany, , 1 Kastor Neurobiology of Aging Laboratories and Fishberg Research Center for Neurobiology and Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York and , 2 MicroBrightField Inc., Williston, VT, USA

Address correspondence to Christoph Schmitz, Department of Anatomy and Cell Biology, RWTH University of Aachen, Wendlingweg 2, D-52057 Aachen, Germany. Email: cschmitz{at}ukaachen.de.

Prenatal X-irradiation, even at doses <1 Gy, can induce spatial disarray of neurons in the brains of offspring, possibly due to disturbed neuronal migration. Here we analyze the effects of prenatal low-dose X-irradiation using a novel stereological method designed to investigate the three-dimensional (3D) spatial arrangement of neurons in thick sections. Pregnant mice were X-irradiated with 50 cGy on embryonic day 13 or were sham-irradiated. The right brain halves of their 180-day-old offspring were dissected into entire series of 150 µm thick frontal cryostat sections and stained with gallocyanin. Approximately 700 layer V pyramidal cells per animal were sampled in a systematic-random manner in the middle of the section’s thickness. The x–y–z coordinates of these ‘parent neurons’ were recorded, as well as of all neighboring (up to 10) ‘offspring neurons’ close to each ‘parent neuron’. From these data, the nearest neighbor distance (NND) distributions for layer V pyramidal cells were calculated. Using this novel 3D analysis method, we found that, in comparison to controls, prenatal X-irradiation had no effect on the total neuron number, but did cause a reduction in the mean volume of layer V by 26.5% and a more dispersed spatial arrangement of these neurons. Considering the recent literature, it seems reasonable to consider abnormal neuronal migration as the potential basic cause of this finding.


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