2D and 3D assessment of neuropathology in rat brain after prenatal exposure to methylazoxymethanol, a model for developmental neurotoxicty.
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.
de Groot
Didima M G
DM
TNO Quality of Life, Utrechtseweg 48, P.O. Box 360, 3700 AJ Zeist, The Netherlands. degroot@chemie.tno.nl
Hartgring
Sarita
S
van de Horst
Linda
L
Moerkens
Marja
M
Otto
Marlies
M
Bos-Kuijpers
Marga H M
MH
Kaufmann
Wolfgang S H
WS
Lammers
Jan H C M
JH
O'callaghan
James P
JP
Waalkens-Berendsen
Ine D H
ID
Pakkenberg
Bente
B
Gundersen
Hansjørgen G
HG
D000014:Abnormalities, Drug-Induced; D000818:Animals; D021461:Animals, Outbred Strains; D001921:Brain / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology; D002452:Cell Count; D005260:Female; D021621:Imaging, Three-Dimensional; D007274:Injections, Intraperitoneal; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
D013723:Teratogens; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol