title: Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.
abstract: In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.
authors: Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors: Iwa
authors: I
authors: Lee
authors: Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors: Per
authors: P
authors: Eriksson
authors: Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors: Anders
authors: A
authors: Fredriksson
authors: Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors: Sonja
authors: S
authors: Buratovic
authors: Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden. Electronic address: henrik.viberg@ebc.uu.se.
authors: Henrik
authors: H
authors: Viberg
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D012721:Carbaryl / Q000737:chemistry / Q000633:toxicity*; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D004390:Chlorpyrifos / Q000737:chemistry / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D010575:Pesticides / Q000633:toxicity*; D018091:Receptors, AMPA / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000110:Acetylcholinesterase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D012721:Carbaryl; D004390:Chlorpyrifos; D002800:Cholinesterase Inhibitors; D000076122:Disks Large Homolog 4 Protein; D019922:GAP-43 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D010575:Pesticides; D018091:Receptors, AMPA; D016708:Synaptophysin; D016875:tau Proteins; C501447:Dlg4 protein, mouse
keywords: Acetylcholinesterase; Behavior; Carbaryl; Chlorpyrifos; Developmental neurotoxicology; Protein