Coding region paraoxonase polymorphisms dictate accentuated neuronal reactions in chronic, sub-threshold pesticide exposure.
Organophosphate pesticides (OPs), known inhibitors of acetylcholinesterase (AChE), are used extensively throughout the world. Recent studies have focused on the ACHE/PON1 locus as a determinant of inherited susceptibility to environmental OP exposure. To explore the relationship of the corresponding gene-environment interactions with brain activity, we integrated neurophysiologic, neuropsychological, biochemical, and genetic methods. Importantly, we found that subthreshold OP exposure leads to discernible physiological consequences that are significantly influenced by inherited factors. Cortical EEG analyses by LORETA revealed significantly decreased theta activity in the hippocampus, parahippocampal regions, and the cingulate cortex, as well as increased beta activity in the prefrontal cortex of exposed individuals-areas known to play a role in cholinergic-associated cognitive functions. Through neuropsychological testing, we identified an appreciable deficit in the visual recall in exposed individuals. Other neuropsychological tests revealed no significant differences between exposed and non-exposed individuals, attesting to the specificity of our findings. Biochemical analyses of blood samples revealed increases in paraoxonase and arylesterase activities and reduced serum acetylcholinesterase activity in chronically exposed individuals. Notably, specific paraoxonase genotypes were found to be associated with these exposure-related changes in blood enzyme activities and abnormal EEG patterns. Thus, gene-environment interactions involving the ACHE/PON1 locus may be causally involved in determining the physiological response to OP exposure.
Browne
R Orie
RO
Department of Physiology, Soroka University Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
Moyal-Segal
Liat Ben
LB
Zumsteg
Dominik
D
David
Yaron
Y
Kofman
Ora
O
Berger
Andrea
A
Soreq
Hermona
H
Friedman
Alon
A
D000110:Acetylcholinesterase / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000235:genetics; D004569:Electroencephalography; D004781:Environmental Exposure / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011939:Mental Recall; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010755:Organophosphates / Q000009:adverse effects; D010575:Pesticides / Q000009:adverse effects*; D011110:Polymorphism, Genetic
D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D010575:Pesticides; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D000110:Acetylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human