title: Prenatal exposure of guinea pigs to the organophosphorus pesticide chlorpyrifos disrupts the structural and functional integrity of the brain.
abstract: This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (25 mg/kg, s.c.) or vehicle (peanut oil) once per day for 10 consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40-45 post-natal days (PND) using the Morris water maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T2-weighted anatomical scans and diffusion kurtosis imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of prenatal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment.
authors.affiliation: Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Mullins
authors.affiliation: Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Core for Translational Research in Imaging, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Su
authors.initials: S
authors.lastname: Xu
authors.affiliation: Division of Translational Toxicology, Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Edna F R
authors.initials: EF
authors.lastname: Pereira
authors.affiliation: Division of Translational Toxicology, Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Pescrille
authors.affiliation: Division of Translational Toxicology, Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Spencer W
authors.initials: SW
authors.lastname: Todd
authors.affiliation: Division of Translational Toxicology, Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Jacek
authors.initials: J
authors.lastname: Mamczarz
authors.affiliation: Division of Translational Toxicology, Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Edson X
authors.initials: EX
authors.lastname: Albuquerque
authors.affiliation: Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Core for Translational Research in Imaging, University of Maryland School of Medicine, Baltimore, MD 21201, United States. Electronic address: rgullapalli@umm.edu.
authors.forename: Rao P
authors.initials: RP
authors.lastname: Gullapalli
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004390:Chlorpyrifos / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects; D056324:Diffusion Tensor Imaging; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006168:Guinea Pigs; D007306:Insecticides / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D062025:Organophosphate Poisoning / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011930:Reaction Time / Q000187:drug effects
chemical_list: D007306:Insecticides; D004390:Chlorpyrifos
keywords: Chlorpyrifos; Diffusion tensor imaging; MRI; Neurodevelopment; Prenatal exposure