Anshuman Singh

Anshuman Singh | Editor

Affilation: Ophthalmology, USA

My PhD dissertation have indicated that prenatal exposure to low doses of the synthetic type II pyrethroid pesticide cypermethrin modify the ontogeny of xenobiotic and endogenous substrate metabolizing CYPs and increase the expression of these CYPs in brain and different brain regions that persisted up to adulthood. The data further demonstrated placental transfer of the pyrethroids even at these low doses, may be sufficient to induce CYPs in the brain regions leading to neurobehavioral alterations of the exposed offsprings. The data indicating persistence in the increase in expression of CYPs in the exposed offsprings, suggests that prenatal exposure of cypermethrin to even low doses may imprint the expression of these CYPs in the liver and brain of the offsprings, enhancing the responsiveness of these CYP isoenzymes when the prenatally exposed offsprings were subsequently rechallenged at adulthood. Epigenetic studies demonstrated decrease in the methylation pattern and subsequent increase in the acetylation pattern in these CYPs, which are necessary for maintaining the imprinted status of genes. Alterations in the circulating level of hormones during postnatal development and when prenatally exposed offsprings were rechallenged at adulthood provided evidence for the imprinting and overexpression of CYP isoenzymes. Further, similarities in the alterations of CYPs and neurotransmitter receptors during postnatal development and given the proximity of neurotransmitter receptors and CYPs within the brain regions have further provided support to the previous reports that these alterations are closely related events. Further, presence of specific sequences found to be involved in regulating the levels of CYPs and rate limiting enzymes that catalyze synthesis of neurotransmitters, suggest that cerebral CYPs are possibly closely associated with neurotransmission pathways. Our data thus indicating imprinting of the cerebral CYP isoenzymes and close association of the alterations in CYPs with neurotransmission processes in the prenatally exposed offsprings could be of immense significance in elucidating the developmental neurotoxicity of environmental chemicals.

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