Prenatal Exposure of Guinea Pigs to the Organophosphorus Pesticide Chlorpyrifos Disrupts the Structural and Functional Integrity of the Brain

Overview

Journal Neurotoxicology

Specialties Environmental Health
Neurology
Toxicology

Date 2015 Feb 24

PMID 25704171

Citations 10

Authors

Roger J Mullins

Su Xu

Edna F R Pereira

Joseph D Pescrille

Spencer W Todd

Jacek Mamczarz

Edson X Albuquerque

Rao P Gullapalli

Affiliations

Soon will be listed here.

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.

Citing Articles

Conductive hearing loss does not affect spatial learning and memory in middle-aged guinea pigs.

Barry K, Jimena J, Tarawneh H, Johnsen W, Osmanbasic A, Rodger J Sci Rep. 2024; 14(1):31103.

PMID: 39730908 PMC: 11680780. DOI: 10.1038/s41598-024-82408-5.

Children's exposure to chemical contaminants: Demographic disparities and associations with the developing basal ganglia.

Fowler C, Reuben A, Stapleton H, Hoffman K, Herkert N, Barakat L Environ Res. 2024; 263(Pt 1):119990.

PMID: 39304016 PMC: 11608154. DOI: 10.1016/j.envres.2024.119990.

Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders.

Piras I, Gabriele S, Altieri L, Lombardi F, Sacco R, Lintas C Antioxidants (Basel). 2021; 10(2).

PMID: 33499329 PMC: 7912005. DOI: 10.3390/antiox10020164.

Gestational exposures to organophosphorus insecticides: From acute poisoning to developmental neurotoxicity.

Todd S, Lumsden E, Aracava Y, Mamczarz J, Albuquerque E, Pereira E Neuropharmacology. 2020; 180:108271.

PMID: 32814088 PMC: 7655673. DOI: 10.1016/j.neuropharm.2020.108271.

Prenatal exposure to organophosphate pesticides and brain morphology and white matter microstructure in preadolescents.

van den Dries M, Lamballais S, El Marroun H, Pronk A, Spaan S, Ferguson K Environ Res. 2020; 191:110047.

PMID: 32805249 PMC: 7657967. DOI: 10.1016/j.envres.2020.110047.

References

Rauh V, Perera F, Horton M, Whyatt R, Bansal R, Hao X . Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci U S A. 2012; 109(20):7871-6. PMC: 3356641. DOI: 10.1073/pnas.1203396109. View

Hunter D, Lassiter T, Padilla S . Gestational exposure to chlorpyrifos: comparative distribution of trichloropyridinol in the fetus and dam. Toxicol Appl Pharmacol. 1999; 158(1):16-23. DOI: 10.1006/taap.1999.8689. View

Fonnum F, Sterri S, Aas P, Johnsen H . Carboxylesterases, importance for detoxification of organophosphorus anticholinesterases and trichothecenes. Fundam Appl Toxicol. 1985; 5(6 Pt 2):S29-38. DOI: 10.1016/0272-0590(85)90112-5. View

Lewejohann L, Pickel T, Sachser N, Kaiser S . Wild genius - domestic fool? Spatial learning abilities of wild and domestic guinea pigs. Front Zool. 2010; 7:9. PMC: 2859863. DOI: 10.1186/1742-9994-7-9. View

Song X, Seidler F, Saleh J, Zhang J, Padilla S, Slotkin T . Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade. Toxicol Appl Pharmacol. 1997; 145(1):158-74. DOI: 10.1006/taap.1997.8171. View

Aldridge J, Meyer A, Seidler F, Slotkin T . Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure. Environ Health Perspect. 2005; 113(8):1027-31. PMC: 1280344. DOI: 10.1289/ehp.7968. View

Cheung M, Hui E, Chan K, Helpern J, Qi L, Wu E . Does diffusion kurtosis imaging lead to better neural tissue characterization? A rodent brain maturation study. Neuroimage. 2009; 45(2):386-92. DOI: 10.1016/j.neuroimage.2008.12.018. View

Mamczarz J, Kulkarni G, Pereira E, Albuquerque E . Galantamine counteracts development of learning impairment in guinea pigs exposed to the organophosphorus poison soman: clinical significance. Neurotoxicology. 2011; 32(6):785-98. PMC: 5673497. DOI: 10.1016/j.neuro.2011.07.001. View

Rauh V, Garfinkel R, Perera F, Andrews H, Hoepner L, Barr D . Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics. 2006; 118(6):e1845-59. PMC: 3390915. DOI: 10.1542/peds.2006-0338. View

10.

Bouchard M, Chevrier J, Harley K, Kogut K, Vedar M, Calderon N . Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. 2011; 119(8):1189-95. PMC: 3237357. DOI: 10.1289/ehp.1003185. View

11.

Sherman J . Chlorpyrifos (Dursban)-associated birth defects: report of four cases. Arch Environ Health. 1996; 51(1):5-8. DOI: 10.1080/00039896.1996.9935986. View

12.

Engel S, Wetmur J, Chen J, Zhu C, Barr D, Canfield R . Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect. 2011; 119(8):1182-8. PMC: 3237356. DOI: 10.1289/ehp.1003183. View

13.

Byrnes M, Reynolds J, Brien J . Effect of prenatal ethanol exposure during the brain growth spurt of the guinea pig. Neurotoxicol Teratol. 2001; 23(4):355-64. DOI: 10.1016/s0892-0362(01)00150-7. View

14.

Levin E, Addy N, Baruah A, Elias A, Christopher N, Seidler F . Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations. Neurotoxicol Teratol. 2002; 24(6):733-41. DOI: 10.1016/s0892-0362(02)00272-6. View

15.

Monnet-Tschudi F, Zurich M, Schilter B, Costa L, Honegger P . Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures. Toxicol Appl Pharmacol. 2000; 165(3):175-83. DOI: 10.1006/taap.2000.8934. View

16.

Altman J, Das G . Postnatal neurogenesis in the guinea-pig. Nature. 1967; 214(5093):1098-101. DOI: 10.1038/2141098a0. View

17.

Li A, Lowe K, McIntosh L, Mink P . Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos developmental neurobehavioral outcomes. J Toxicol Environ Health B Crit Rev. 2012; 15(2):109-84. PMC: 3386549. DOI: 10.1080/10937404.2012.645142. View

18.

Hui E, Cheung M, Qi L, Wu E . Towards better MR characterization of neural tissues using directional diffusion kurtosis analysis. Neuroimage. 2008; 42(1):122-34. DOI: 10.1016/j.neuroimage.2008.04.237. View

19.

Mullins R, Xu S, Pereira E, Mamczarz J, Albuquerque E, Gullapalli R . Delayed hippocampal effects from a single exposure of prepubertal guinea pigs to sub-lethal dose of chlorpyrifos: a magnetic resonance imaging and spectroscopy study. Neurotoxicology. 2013; 36:42-8. PMC: 3669662. DOI: 10.1016/j.neuro.2013.02.002. View

20.

Chida Y, Kokubo Y, Sato S, Kuge A, Takemura S, Kondo R . The alterations of oligodendrocyte, myelin in corpus callosum, and cognitive dysfunction following chronic cerebral ischemia in rats. Brain Res. 2011; 1414:22-31. DOI: 10.1016/j.brainres.2011.07.026. View