The mRNA expression and histological integrity in rat forebrain motor and sensory regions are minimally affected by acrylamide exposure through drinking water

Journal Article · Sun Nov 01 04:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.07.036· OSTI ID:21344780

Latendresse, John R ^[1]; Delongchamp, Robert R ^[2]; Warbritton, Alan R ^[1]; Thomas, Monzy ^[3]; Divine, Becky ^[1]; Doerge, Daniel R ^[4]

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1. Toxicologic Pathology Associates, 3900 NCTR Road, Jefferson, AR 72079 (United States)
2. Department of Epidemiolgoy, University of Arkansas for Medical Sciences, College of Public Health, 4301 W. Markham St., 820, Little Rock, AR 72205 (United States)
3. US Food and Drug Administration, National Center for Toxicological Research, Division of Neurotoxicology, 3900 NCTR Road, Jefferson, AR 72079 (United States)
4. US Food and Drug Administration, National Center for Toxicological Research, Division of Biochemical Toxicology, 3900 NCTR Road, Jefferson, AR 72079 (United States)

A study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum, substantia nigra and parietal cortex of rat after a 2-week acrylamide exposure. The highest dose tested (maximally tolerated) of approximately 44 mg/kg/day resulted in a significant decreased body weight, sluggishness, and locomotor activity reduction. These physiological effects were not accompanied by prominent changes in gene expression in the forebrain. All the expression changes seen in the 1200 genes that were evaluated in the three brain regions were <= 1.5-fold, and most not significant. Very few, if any, statistically significant changes were seen in mRNA levels of the more than 50 genes directly related to the cholinergic, noradrenergic, GABAergic or glutamatergic neurotransmitter systems in the striatum, substantia nigra or parietal cortex. All the expression changes observed in genes related to dopaminergic function were less than 1.5-fold and not statistically significant and the 5HT1b receptor was the only serotonin-related gene affected. Therefore, gene expression changes were few and modest in basal ganglia and sensory cortex at a time when the behavioral manifestations of acrylamide toxicity had become prominent. No histological evidence of axonal, dendritic or neuronal cell body damage was found in the forebrain due to the acrylamide exposure. As well, microglial activation was not present. These findings are consistent with the absence of expression changes in genes related to changes in neuroinflammation or neurotoxicity. Over all, these data suggest that oral ingestion of acrylamide in drinking water or food, even at maximally tolerable levels, induced neither marked changes in gene expression nor neurotoxicity in the motor and somatosensory areas of the central nervous system.

• OSTI ID: 21344780
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 240; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACRYLAMIDE
AMIDES
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DOPAMINE
DOSES
DRINKING WATER
DRUGS
GENES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
MAMMALS
MESSENGER-RNA
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHENOLS
POLYPHENOLS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
RESPONSE MODIFYING FACTORS
RNA
RODENTS
SEROTONIN
SOMATIC CELLS
SYMPATHOMIMETICS
TOXICITY
TRYPTAMINES
VERTEBRATES
WATER