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

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Groot, D.M.G. de

Hartgring, S.

Horst, L. van de

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.
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.
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Toxicology and Applied PharmacologyCerebellumDevelopmental neurotoxicityHippocampusLinear morphometryMethylazoxymethanolNeuron numbersRatStereologyMethylazoxymethanolAnimal experimentAnimal modelAnimal tissueBrain developmentBrain sizeBrain weightCell countCell proliferationCell structureCerebellumControlled studyDevelopmental disorderEvaluationFemaleHippocampusLinear systemMaleMorphometricsNeuropathologyNeurotoxicityNonhumanPregnancyPrenatal exposureProgenyPyramidal nerve cellQuantitative analysisRatStereologyStrengthThree dimensional imagingAbnormalities, Drug-InducedAnimalsAnimals, Outbred StrainsBrainCell CountFemaleImaging, Three-DimensionalInjections, IntraperitonealMaleMaternal ExposureMethylazoxymethanol AcetateOrgan SizePregnancyPrenatal Exposure Delayed EffectsRatsRats, WistarSpecific Pathogen-Free OrganismsTeratogensToxicity Tests
TNO Identifier
238697
Repository link
https://resolver.tno.nl/uuid:4d5e20d9-00fa-4043-970a-2b6b85598c05
ISSN
08906238
Source
Reproductive Toxicology, 20(3), pp. 417-432.
Pages
417-432
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