title: Neurobehavioral and transcriptional effects of acrylamide in juvenile rats.
abstract: Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in juvenile rats. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of a few genes that are involved in muscle contraction, pain, and dopaminergic neuronal pathways. First, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified a few genes previously not implicated in acrylamide neurotoxicity that might be further developed into biomarkers for assessing the risk of adverse health effects induced by acrylamide exposure.
authors.affiliation: Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Seale
authors.forename: Qin
authors.initials: Q
authors.lastname: Feng
authors.forename: Ameeta K
authors.initials: AK
authors.lastname: Agarwal
authors.forename: Abir T
authors.initials: AT
authors.lastname: El-Alfy
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D018737:Hand Strength / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D008297:Male; D046228:Microarray Analysis; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D020106:Acrylamide; D012313:RNA