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

Food Chem Toxicol. 2015 Mar:77:74-81. doi: 10.1016/j.fct.2014.12.010. Epub 2015 Jan 5.

Abstract

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.

Keywords: Cytochrome P450s; Expression; Lindane; Neurotransmitter receptors; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Carrier Proteins
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation
  • Hexachlorocyclohexane / toxicity*
  • Insecticides / toxicity*
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A / genetics
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Receptors, Neurotransmitter / genetics
  • Receptors, Neurotransmitter / metabolism
  • Synaptic Transmission / drug effects

Substances

  • Carrier Proteins
  • Insecticides
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2
  • Receptors, GABA-A
  • Receptors, Neurotransmitter
  • Hexachlorocyclohexane
  • Cytochrome P-450 Enzyme System