Acrylamide neurotoxicity: neurological, morhological and molecular endpoints in animal models.
Acrylamide (AA) monomer is used in numerous chemical industries and is a contaminant in potato- and grain-based foods prepared at high temperatures. Although experimental animal studies have implicated carcinogenicity and reproductive toxicity as possible consequences of exposure, neurotoxicity is the only outcome identified by epidemiological studies of occupationally exposed human populations. Neurotoxicity in both humans and laboratory animals is characterized by ataxia and distal skeletal muscle weakness. Early neuropathological studies suggested that AA neurotoxicity was mediated by distal axon degeneration. However, more recent electrophysiological and quantitative morphometric analyses have identified nerve terminals as primary sites of AA action. A resulting defect in neurotransmitter release appears to be the pathophysiological basis of the developing neurotoxicity. Corresponding mechanistic research suggests that AA impairs release by adducting cysteine residues on functionally important presynaptic proteins. In this publication we provide an overview of recent advances in AA research. This includes a discussion of the cumulative nature of AA neurotoxicity and the putative sites and molecular mechanisms of action.
LoPachin
Richard M
RM
Department of Anesthesiology, Albert Einstein College of Medicine, 111 E. 210th st., Bronx, NY 10467, USA. lopachin@aecom.yu.edu
D020106:Acrylamide / Q000633:toxicity*; D000178:Acrylamides; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002617:Chemical Industry; D003545:Cysteine / Q000737:chemistry; D004195:Disease Models, Animal; D004594:Electrophysiology; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology; D009410:Nerve Degeneration; D009422:Nervous System Diseases; D009474:Neurons / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009498:Neurotoxins; D051381:Rats; D013696:Temperature; D013997:Time Factors
D000178:Acrylamides; D009498:Neurotoxins; D020106:Acrylamide; D003545:Cysteine