Title
2D and 3D assessment of neuropathology in rat brain after prenatal exposure to methylazoxymethanol, a model for developmental neurotoxicty
Author
de Groot, D.M.G.
Hartgring, S.
van de Horst, L.
Moerkens, M.
Otto, M.
Bos-Kuijpers, M.H.M.
Kaufmann, W.S.H.
Lammers, J.H.C.M.
O'Callaghan, J.P.
Waalkens-Berendsen, I.D.H.
Pakkenberg, B.
Gundersen, H.G.
TNO Kwaliteit van Leven
Publication year
2005
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. © 2005 Elsevier Inc. All rights reserved.
Subject
Biology
Toxicology and Applied Pharmacology
Cerebellum
Developmental neurotoxicity
Hippocampus
Linear morphometry
Methylazoxymethanol
Neuron numbers
Rat
Stereology
methylazoxymethanol
animal experiment
animal model
animal tissue
article
brain development
brain size
brain weight
cell count
cell proliferation
cell structure
cerebellum
controlled study
developmental disorder
evaluation
female
hippocampus
linear system
male
morphometrics
neuropathology
neurotoxicity
nonhuman
pregnancy
prenatal exposure
progeny
pyramidal nerve cell
quantitative analysis
rat
stereology
strength
three dimensional imaging
Abnormalities, Drug-Induced
Animals
Animals, Outbred Strains
Brain
Cell Count
Female
Imaging, Three-Dimensional
Injections, Intraperitoneal
Male
Maternal Exposure
Methylazoxymethanol Acetate
Organ Size
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Rats, Wistar
Specific Pathogen-Free Organisms
Teratogens
Toxicity Tests
To reference this document use:
http://resolver.tudelft.nl/uuid:4d5e20d9-00fa-4043-970a-2b6b85598c05
DOI
https://doi.org/10.1016/j.reprotox.2005.04.006
TNO identifier
238697
ISSN
0890-6238
Source
Reproductive Toxicology, 20 (3), 417-432
Document type
article