Effect of Gestational Exposure of Cypermethrin on Postnatal Development of Brain Cytochrome P450 2D1 and 3A1 and Neurotransmitter Receptors
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Oral administration of low doses (1.25, 2.5, or 5 mg/kg) of cypermethrin to pregnant Wistar rats from gestation days 5 to 21 led to dose-dependent differences in the induction of cytochrome P450 2D1 (CYP2D1) and 3A1 messenger RNA (mRNA) and protein in brain regions isolated from the offsprings postnatally at 3 weeks that persisted up to adulthood (12 weeks). Similar alterations were observed in the expression of GABAergic, muscarinic, dopaminergic, and serotonergic neurotransmitter receptors in brain regions of rat offsprings. Rechallenge of the prenatally exposed offsprings at adulthood (12 weeks old) with cypermethrin (p.o., 10 mg/kg for 6 days) led to a greater magnitude of alterations in the expression of CYPs, neurotransmitter receptors, and neurotransmitter receptor binding in the brain regions when compared to the control offsprings treated at adulthood with cypermethrin or prenatally exposed offsprings. A greater magnitude of decrease was also observed in the spontaneous locomotor activity (SLA) in prenatally exposed offsprings rechallenged with cypermethrin. The present data indicating similarities in the alterations in the expression of CYPs (2D1 and 3A1) and neurotransmitter receptors in brain has led us to suggest that endogenous function regulating CYPs is possibly associated with neurotransmission processes. A greater magnitude of alterations in CYP2D1, 3A1, neurotransmitter receptors, and SLA in rechallenged animals has further provided evidence that alterations in CYPs are possibly linked with neurotransmission processes.
KeywordsCYPs Neurotransmitter receptors Gestation Rechallenge Behavior
The authors are grateful to the Director, CSIR—Indian Institute of Toxicology Research, Lucknow, for his keen interest and support in carrying out the study. AS is thankful to CSIR, N. Delhi for providing Senior Research Fellowship. The financial assistance of the Department of Biotechnology, N. Delhi is also gratefully acknowledged.
Conflict of Interest
The authors declare that they have no competing financial interests.
- 3.Eriksson P (1996) Developmental neurotoxicity of environmental agents in the neonate. Neurotoxicology 18(3):719–726Google Scholar
- 7.Ray DE, Ray D, Forshaw PJ (2000) Pyrethroid insecticides: poisoning syndromes, synergies, and therapy. Clin Toxicol 38(2):95–101Google Scholar
- 55.Niznik HB, Tyndale RF, Sallee FR, Gonzalez FJ, Hardwick JP, Inaba T, Kalow W (1990) The dopamine transporter and cytochrome P450IID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct [3H]GBR-12935 binding proteins. Arch Biochem Biophys 276(2):424–432CrossRefPubMedGoogle Scholar