Role of ornithine decarboxylase and the polyamines in nervous system development: A review |
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| Authors: | Theodore A. Slotkin Jorge Bartolome |
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| Affiliation: | 1. Department of General Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA;2. Department of Cytogenetics/Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA;3. Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA;4. Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, IA, USA;5. Department of Thoracic Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA;1. Department of Neuroscience, Carleton University, Ottawa, ON, Canada;2. Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil;3. Department of Physiology, São Paulo State University, Botucatu, SP, Brazil;4. Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil;1. Department of Chemistry, Cape-Peninsula University of Technology, P.O. Box 652, Capetown, 8000, South Africa;2. Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, Kerala- 686560, India.;3. Department of Applied Chemistry, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, Johannesburg, South Africa.;4. School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala-686560, India.;5. School of Chemical Sciences, Mahatma Gandhi University, Kottayam, Kerala-686560, India.;1. Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China;2. Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China;3. Information Security and Big Data Research Institute, Central South University, Changsha, Hunan, People’s Republic of China |
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| Abstract: | Development of nervous tissue is controlled, in part, by the ornithine decarboxylase (ODC)/polyamine system. Each brain region possesses a unique ontogenetic pattern for ODC, with highest levels of the enzyme associated with periods of most rapid growth. For this reason, perturbation of the ODC profile has proven useful in examinations of teratologic mechanisms and detection of adverse environmental effects during development. More recently, the replication of neuronal cells in developing brain has been shown to require the maintenance of polyamine levels and consequently, depletion of polyamines by alpha-difluoromethylornithine (DFMO, an ODC inhibitor) arrests brain cell maturation. DFMO also interferes with neuronal migration, axonogenesis and synaptogenesis, leading to disruption of the cytoarchitectural organization of brain structures: these results imply a similarly important role for polyamines in post-replicative events. Indeed, [3H]DFMO-autoradiographic localization of ODC in developing cerebellar lamina indicates high levels of activity associated with neuropil, areas of axonal outgrowth, and post-mitotic granule cells. Axonal outgrowth during regeneration after nerve damage in the mature nervous system may display some of the same characteristics as in developing neurons, suggesting that the two processes share common polyamine-dependent mechanisms. |
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| Keywords: | Ornithine decarboxylase Polyamines Development α -Difluoromethylornithine Synaptogenesis |
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