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Effects of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase, on nucleic acids and proteins in developing rat brain: critical perinatal periods for regional selectivity.
- Source :
-
Neuroscience [Neuroscience] 1986 Feb; Vol. 17 (2), pp. 399-407. - Publication Year :
- 1986
-
Abstract
- Ornithine decarboxylase and its metabolic products, the polyamines, are known to coordinate macromolecule synthesis in developing neural tissues; consequently, inhibition of this enzyme by alpha-difluoromethylornithine interferes with cellular replication and differentiation. We examined the regional selectivity of the effect of alpha-difluoromethylornithine administered either postnatally (days 1-19) or during gestation (days 15-17), in order to determine whether specific phases of maturation are particularly sensitive to polyamine depletion. In the cerebellum, which undergoes major phases of replication and differentiation after birth, postnatal alpha-difluoromethylornithine administration caused a profound and progressive deficit in tissue weight gain as well as in DNA, RNA and protein content. Although regions which develop earlier (cerebral cortex, midbrain + brain stem) also showed adverse effects of postnatal alpha-difluoromethylornithine, the deficits were of much smaller magnitude and were comparable to the effect of the drug on general body growth. Despite these regional differences, inhibition of DNA synthesis ([3H]thymidine incorporation) was similar in cerebellum and in midbrain + brain stem, indicating that the direct impact of alpha-difluoromethylornithine-induced polyamine depletion is exerted in both; DNA synthesis in cerebral cortex was spared relative to the other two regions. These data suggested that the impact of alpha-difluoromethylornithine on development depends, in part, upon the relative degree of maturation of each brain region at the time of drug exposure. In confirmation of this hypothesis, prenatal alpha-difluoromethylornithine given on gestational days 15-17 resulted in loss of the specificity toward cerebellar development and enhancement of effects on cerebral cortex, the region which had displayed the least sensitivity to postnatal alpha-difluoromethylornithine.
- Subjects :
- Aging
Animals
Body Weight
Brain drug effects
Brain enzymology
Eflornithine
Female
Injections, Subcutaneous
Organ Size
Ornithine administration & dosage
Ornithine pharmacology
Ornithine Decarboxylase Inhibitors
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Brain growth & development
DNA metabolism
Nerve Tissue Proteins metabolism
Ornithine analogs & derivatives
Ornithine Decarboxylase physiology
RNA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 2422585
- Full Text :
- https://doi.org/10.1016/0306-4522(86)90255-1