Mohamed Bahie Abou-Donia
Professor of Pharmacology and Cancer Biology

The overall research program in this laboratory is directed toward understanding the basic mechanisms by which chemicals adversely affect the nervous system. This should lead to a better assessment of acute and chronic neurotoxicities and the development of drugs to prevent or treat them. We are primarily concerned with neurotoxicants that produce Wallerian-type degeneration of the axon and myelin of the central and peripheral nervous systems. These chemicals include antiesterase organophosphorus compounds, aliphatic hydrocarbons, acrylamide, and carbon disulfide. These studies are being carried out in vivo and in vitro using cell culture systems, i.e., primary cultures of bovine adrenomedullary chromaffin cells and the rat pheochromocytoma PC 12 cells.

The role of kinase-dependent phosphorylation of cytoskeletal proteins in the pathogenesis of these neurotoxicants is being studied. The involvement of calcium-Calmodulin kinase II in the mechanism of organophosphorus compound-induced delayed neurotoxicity is under investigation. We are studying the multiple mechanisms responsible for the accumulation of neurofilaments above nodes of Ranvier in the distal axon, a pathognomonic feature of aliphatic hexacarbon- and acrylamide-induced neurotoxicities, i.e., inhibition of a kinase inhibition of a protease, or crosslinking of neurofilaments.

We are also examining the role of pharmacokinetics and metabolism of neurotoxicants in age-sensitivity and species selectivity that are characteristic of these neuropathies. The metabolic activation and inactivation of neurotoxic chemicals by specific cytochrome P-450 isozymes are being investigated.

An interesting characteristic of neurotoxic chemicals that induce Wallerian-type degeneration of the nervous system is the ability to cause male reproductive toxicity. Recently, we have confirmed this phenomenon with organophosphorus compounds and characterized the male reproductive toxicity of tri-o-cresyl phosphate.

Recently, we have been investigating the mechanisms that may be involved in the Persian Gulf War Veterans' illnesses. We are studying the hypothesis that this condition is related to the acute cholinergic and delayed neurotoxicity resulting from coexposure to multiple chemicals including organophosphorus esters and prophylactic treatments with various drugs. Our previous studies have demonstrated that combined exposure to large doses of chemicals produced greater toxicity than that produced by single components. In March of this year, we were awarded a grant from the Department of Defense to expand our previous findings to include doses low enought to be representative of human exposure levels. We are investigating the long term effects of sub-clinical exposure to the nerve agent, saran, along and in combination with the prophylactic drug, pyridostigmine burmide and the insect repellant DEET as well as the insecticide permethrin in the presence or absence of stress. Neurologic defects are being evaluated by clinical condition, neurobehavior, integrity of teh blood brain barrier, and electrophysiological changes. We also plan to study the effect of these treatments on the level of actylcholinestisase as well as the cholinergic expression.

Current Appointments & Affiliations

Contact Information

  • 308 Research Drive, Room C173, Durham, NC 27710
  • Duke Box 3813, Durham, NC 27710

Some information on this profile has been compiled automatically from Duke databases and external sources. (Our About page explains how this works.) If you see a problem with the information, please write to Scholars@Duke and let us know. We will reply promptly.