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2D and 3D assessment of neuropathology in rat brain after prenatal exposure to methylazoxymethanol, a model for developmental neurotoxicity.

Authors
DeGroot-DMG; Hartgring-S; Van de Horst-L; Moerkens-M; Otto-M; Bos-Kuijpers-MHM; Kaufmann-WSH; Lammers-JHCM; O'Callaghan-JP; Waalkens-Berendsen-IDH; Pakkenberg-B; Gundersen-HG
Source
Reprod Toxicol 2005 Sep/Oct; 20(3):417-432
NIOSHTIC No.
20028144
Abstract
To evaluate the ability of a tiered quantitative morphological approach to reveal developmental neurotoxicity, morphometric parameters were measured in the offspring of rats treated with methylazoxymethanol (MAM) during days 13-15 of pregnancy. Treatment was aimed at inhibiting the proliferation phase of hippocampal neurons while leaving cerebellar neurons unaffected. 2D and 3D assessment of brain morphology combined with straightforward measurement of brain size, weight and volume, and the usefulness of estimation of total neuron numbers were studied. Each tier indicated major effects of MAM, from macroscopic effects in the cerebrum (first tier) to a considerable loss of neurons in the hippocampal CA1 pyramidal layer (third tier). The cerebellum and the number of cerebellar granular neurons were not changed. Along with each step of the proposed tiered approach (brain size -> linear morphometry -> stereology), the discriminative strength of the endpoints, and thus the probability to pinpoint the extent and location of developmental brain lesions increased.
Keywords
Quantitative-analysis; Morphology; Neurotoxic-effects; Neurotoxicity; Neurotoxicology; Neurotoxins; Animal-studies; Animals; Laboratory-animals; Toxic-effects; Toxic-materials; Toxins; Brain-damage; Brain-disorders; Brain-tumors
Contact
de Groot DMG, TNO, Qual Life, Utrechtseweg 48,POB 360, NL-3700 AJ Zeist, Netherlands
CODEN
REPTED
Publication Date
20050901
Document Type
Journal Article
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0890-6238
NIOSH Division
HELD
Source Name
Reproductive Toxicology
State
WV
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