Duke University Medical Ctr.
Durham, NC 27710
Email: aboud001 AT mc DOT duke DOT edu
Pharmacology & Cancer Biology, School of Medicine
Some chemicals induce neurodegenerative disorders. Examples of these are organophosphorus compounds (Ops), such as the nerve agent sarin. The action of these compounds is related to their ability to phosphorylated 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 Ca+ 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.
Ph.D., University of California, Berkeley, Agricultural Chemistry, 1967
B.S., Alexandria University (Egypt), Agricultural Chemistry, 1960
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.
Abou-Donia, M.B., Goldstein, L.B., Bullman, S., Tu,T., Khan, W.A, Dechkovskaia, A.M., and Abdel-Rahman, AA. (2008). Imidacloprid induces neurobehavioral deficits and increases expression of glial fibrillary acidic protein in the motor cortex and hippocampus in offspring rats following in utero exposure. J. Toxicol. Environ. Health 71: 119-130.
Abou-Donia, M.B., Khan, W.A., Dechkovskaia, A.M. Goldstein L.B. , Bullman, S.L., and Abdel-Rahman , A.A.(2006). In utero exposure to nicotine and chlorpyrifos, alone and in combination produced persistent sensorimotor deficits and Purkinje neuronal loss in the cerebellum of adult offspring rats. J. Toxicol. Environ. Health 80: 620-631.
Damodaran T.V., Patel, A.G., Greenfield, S.T., Dressman, H.K., Lin, S.A., and Abou-Donia, M.B. (2006). Toxicogenomic studies of the vrat brain at an early time point following acute sarin exposure. Neurochem. Res. 31:367-381.
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