The contribution of primary and secondary neuronal degeneration to prenatally-induced micrencephaly.
Prenatal exposure of rats to the alkylating agent methylazoxymethanol acetate (MAM Ac) induces severe micrencephaly in the offspring. The aim of the present study was to examine the contribution of primary cell death (due to a direct action of MAM Ac on the neuroepithelium), and secondary (target-dependent) cell death to the subsequent cell deficits in the visual system following prenatal exposure to MAM Ac on embryonic day 11, 12, 13, 14, 15 or 16. The results showed that when primary cell death substantially reduced the neuronal population of a target structure then there was increased target-dependent cell death in the neurons which normally project to that target. This was particularly evident in the dorsal lateral geniculate nucleus following exposure to MAM Ac on E15. Although the MAM Ac caused virtually no primary cell death in the embryonic precursor cells of the dLGN, the nucleus in the adult offspring was reduced by 87% compared with controls. This reduction was shown to be due to increased postnatal target-dependent, or secondary, cell death due to a severe reduction in layers III and IV of the occipital cortex. The cortical damage was due to primary cell death. Hence, primary cell death only partly accounts for the degree of micrencephaly seen in the offspring, consideration of secondary cell death is necessary to understand the total deficit.
Ashwell
K W
KW
Department of Anatomy, University of Sydney, N.S.W., Australia.
Webster
W S
WS
D000818:Animals; D002470:Cell Survival; D002540:Cerebral Cortex / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D008831:Microcephaly / Q000139:chemically induced*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects; D013477:Superior Colliculi / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects
D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol