Neurobehavioral and transcriptional effects of acrylamide in juvenile rats. Pharmacol Biochem Behav 2012 Mar;101(1):77-84
Date
12/27/2011Pubmed ID
22197712DOI
10.1016/j.pbb.2011.12.006Scopus ID
2-s2.0-84855805905 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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.
Author List
Seale SM, Feng Q, Agarwal AK, El-Alfy ATAuthor
Abir El-Alfy PhD Assistant Dean, Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcrylamideAnimals
Behavior, Animal
Cerebellum
DNA, Complementary
Hand Strength
Hindlimb
Male
Microarray Analysis
Motor Activity
Muscle Strength
Nerve Tissue Proteins
Nervous System
RNA
Rats
Rats, Wistar
Real-Time Polymerase Chain Reaction
Sciatic Nerve
Spinal Cord
Transcription, Genetic
Weight Gain