Bahie M. Abou-Donia, Ph.D.

Bahie M. Abou-Donia Professor of Pharmacology and Cancer Biology
Professor of Neurobiology

Duke University School of Medicine
Box 3813
Durham, NC 27710

Phone: 919-684-2221

Research Interests

Organophosphorus compounds (Ops) induce neurodegenerative disorders. This action is related to their ability to phosphorylate target proteins. Ops have three distinct actions: 1) Cholinergic neurotoxicity resulting from inhibition of acetylcholinesterase (AChE), 2) Organophosphorus ester-Induced Delayed Neurotoxicity (OPIDN), and 3) Organophosphorus ester-Induced Chronic Neurotoxicity (OPICN). Our recent studies using gene expression of rat brain, 15 min and 3 months after exposure to sarin, elucidated the sarin-induced neurotoxicity. A lethal dose of sarin caused up-regulation of nicotinic, muscarinic, GABAnergic and glutamergic receptors, consistent with the activation of glutamate receptors leading to the release of l-glutamate amino acid and activation of NMDA receptor resulting in massive Ca2+ influx and neuronal cell death. Calcium calmodulin kinase II was up-regulated in brain regions that are sensitive to OPIDN. This enzyme that is involved with glutamate receptors in the process of learning and memory is activated by Ca2+ influx through NMDA receptors resulting in mitochondrial dysfunction and free radical formation, followed by caspase activation and apoptotic cell death.

Representative Publications

Abdel-Rahman, A.A., Shetty, A.K. , and Abou-Donia, M.B. (2002) Acute exposure to sarin increases blood brain barrier permeability and induces neuropathological changes in the rat brain: dose-responsed relationship. Neuroscience 113: 721-741.

Abdel-Rahman, A.A. Shetty, A.K. and Abou-Donia, M.B. (2002) Disruption of blood brain barrier and neuronal cell death in cingulated cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome. Neurobiol. Disease 10: 306-326.

Abou-Donia, M. B. (2003). Organophosphorus ester-induced chronic neurotoxicity. Arch. Environ. Health. 58: 484-497.

Damodaran T.V., Patel, A.G., Greenfield, S.T., Dressman, H.K., Lin, S.A., and Abou-Donia, M.B. (2006) Gene expression profiles in the rat brain both immediately and three months following acute sarin exposure. Biochem. Pharmacol. 71:497-520.

Damadaran, TV, Gupta, RP, Attia, MKM, and Abou-Donia, MB (2009) Involvement of Protein Kinase A (PKA)/Phosphorylated CREP (p-CREP) Pathway in the Development of Delayed Neurotoxicit (OPIDN) Induced by O,O-diisopropylphosphoro-fluoridate (DFP) in hens. Toxicol Appl Pharmacol 240:132-142.

Damadaran, TV, Attia, MKM, and Abou-Donia, MB (2011) Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters. Toxicol Appl Pharmacol 256(3):348-359.