Selective ablation of neurons by methylazoxymethanol during pre- and postnatal brain development. 1986

S Chen, and D E Hillman

Neonatal or pregnant albino rats were injected with either single or double doses of methylazoxymethanol (20 mg/kg) to test the temporal specificity of its effect on clearly definable regions of the brain. A single dose, to dams from gestational day 11 to 21 (G11-G21) and to neonatal rats from birth to postnatal day 5 (P0-P5), produced differential weight reductions among various brain regions. Two prominent peaks of reduction were found: one occurring between G13 and G15 for the cerebrum and hippocampus and one occurring between P0 and P1 for the cerebellum and olfactory bulbs. Dual injections of the drug on G14 and G15 produced 60% weight reduction in the cerebrum, and slightly earlier injections on G13 and G14 reduced the weight of the cerebellum by about 23%. This weight reduction was accompanied by narrowing of the cerebellar width, which we believe was due to fewer Purkinje cells. Dual injections of methylazoxymethanol at P0 and P1 reduced the weight of the olfactory bulb by 65%, the cerebellum by 62%, and the hippocampus by 18%. These results show that its short action is within the window of cell division for various neurons and becomes additive on two successive days. This precise toxic effect on brain development can be used to disproportionally reduce the number of neuroblasts in specific regions of the brain. A differential ablation allows analysis of plasticity on pyramidal and nonpyramidal cells of the neocortex and hippocampus, Purkinje and granule cells of the cerebellum, and the granule and mitral cells of the olfactory bulbs.

UI MeSH Term Description Entries
D008746 Methylazoxymethanol Acetate The aglycone of CYCASIN. It acts as a potent carcinogen and neurotoxin and inhibits hepatic DNA, RNA, and protein synthesis. (Methyl-ONN-azoxy)methanol Acetate,Acetate, Methylazoxymethanol
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005260 Female Females
D005314 Embryonic and Fetal Development Morphological and physiological development of EMBRYOS or FETUSES. Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001391 Azo Compounds Organic chemicals where aryl or alkyl groups are joined by two nitrogen atoms through a double bond (R-N Azo Dye,Azo Dyes,Compounds, Azo,Dye, Azo,Dyes, Azo

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