Effect of prenatal exposure of lindane on alterations in the expression of cerebral cytochrome P450s and neurotransmitter receptors in brain regions

• Prenatal exposure of lindane induces overexpression of CYPs in brain regions.
• Similar increase was also observed in the neurotransmitter receptors in offsprings.
• Data suggest association of CYPs with neurotransmission pathways.

Prenatal exposure to low doses (0.0625- or 0.125- or 0.25 mg/kg b. wt., orally) of lindane, an organochlorine insecticide, from gestation day (GD) 5–21 was found to produce a dose-dependent increase in the mRNA expression of cytochrome P450s (CYPs) and associated transcription factors in frontal cortex, cerebellum and corpus striatum isolated from the offsprings. Though the increase in the expression persisted up to postnatal day 60, the increase was significant at postnatal days 21-, and 45- in the offsprings exposed prenatally to relatively higher doses (0.125- or 0.25 mg/kg) of lindane and even up to postnatal day 60 in the offsprings exposed prenatally to the highest dose of lindane. A similar increase in the expression of dopamine D2, 5HT2A and GABAA receptors and associated neurotransmitter receptor binding was observed in the brain regions of the exposed offsprings. Scatchard analysis also suggested an increase in the levels of these neurotransmitter receptors in offsprings prenatally exposed to lindane. The data indicating similarities in the alterations of neurotransmitter receptors and CYPs in brain regions in prenatally exposed offsprings have suggested that neurotransmission processes and CYPs are closely linked that will eventually help in understanding the developmental neurotoxicity of lindane.