Direct and indirect effects on the lateral geniculate nucleus neurons of prenatal exposure to methylazoxymethanol acetate.
In this study the morphology of the lateral geniculate nucleus and occipital cortex in rats with methylazoxymethanol acetate (MAM Ac)-induced micrencephaly was examined. The aim was to examine the relative contributions of (a) the direct cytotoxic action of the drug on precursors of dorsal lateral geniculate nucleus (dLGN) neurons in the fetal brain and, (b) the postnatal degeneration of the dLGN following prenatal destruction of target neurons in the occipital cortex, to the final extent of damage to the dLGN. Exposure to MAM Ac on E13 produced severe necrosis in the fetal thalamus and caused a 77% deficit in neuronal numbers in the mature dLGN. Exposure to MAM Ac on E15 did not cause necrosis in the fetal thalamus but when animals exposed at this time were examined at 5 weeks postnatal age there was an 87% deficit in neuronal numbers in the dLGN. The hypothesis that this deficit was the result of postnatal death of the dLGN neurons following the destruction by MAM Ac of their normal target population in laminae iii and iv of the occipital cortex was supported by the observation of severe postnatal degeneration in the dLGN of animals exposed to MAM Ac on E15. The significance of these direct and indirect effects of the cytotoxic teratogen, MAM Ac, for understanding the mechanisms by which brain abnormalities in human micrencephaly are produced is discussed.
Ashwell
K
K
Department of Anatomy, University of Sydney, N.S.W., Australia.
D000367:Age Factors; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D005260:Female; D005829:Geniculate Bodies / Q000187:drug effects / Q000473:pathology*; D008746:Methylazoxymethanol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009778:Occipital Lobe / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate