The effects of pre- and perinatal nicotine exposure and genetic background on histological and behavioural phenotypes

• Main Author: Balsevich, Georgia Ann
• Language: English
• Published: University of British Columbia 2012
• Online Access: http://hdl.handle.net/2429/41700

Approximately 11% of pregnant woman in Canada continue to use tobacco during pregnancy. Maternal tobacco use increases the risk of complications in pregnancy and also the risk of adverse foetal outcomes. Although tobacco smoke contains over 4000 compounds, studies have established nicotine as the principal component of tobacco smoke that leads to the majority of negative reproductive outcomes associated with maternal tobacco use. It appears the neuroteratogenicity of nicotine is mediated by complex gene-environment interactions. Genetic background contributes to individual differences in nicotine-related phenotypes. The aim of the current study was to investigate the interaction between pre- and perinatal nicotine exposure and genetic background on histological and behavioural measures using DBA/2J (D2) and C57BL/6J (B6) inbred mice. Alterations in neuronal cell populations, regional brain volumes, and behaviour - open field (OF) activity, novel object recognition (NOR), elevated plus maze (EPM), and passive avoidance (PA) - were evaluated on postnatal day (PN) 24 and PN75, following early exposure to nicotine solution (200 μg/ml)starting from 30 days before pregnancy up to pups weaning. Data revealed no difference between treatment groups of dams in gestational weight gain or pup mortality. Histological data showed that early nicotine exposure resulted in decreased striatal volume among preadolescent females and reduced neuronal number within the striatum of preadolescent B6 mice. In the hippocampus the effects of early nicotine exposure appeared more subtle, in which only the granule cell layer of the dentate gyrus in D2 preadolescents was afflicted. Behavioural data showed that early nicotine exposure promoted hyperactivity in D2 female mice and disrupted NOR and PA memory. Specifically, NOR deficits were significant amongst adult male mice whereas PA deficits were unconditional. These data suggest that pre- and perinatal nicotine affects regional brain morphology and leads to neurobehavioural alterations. The observed treatment interactions suggest that genetic background, developmental stage, and sex interact with nicotine to influence nicotine-related phenotypes. === Medicine, Faculty of === Graduate