| Abstract No.: | B-A2006 |
| Country: | Canada |
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| Title: | INCREASED NEWBORN CELL SURVIVAL IN THE ADULT HIPPOCAMPUS FOLLOWING CHRONIC DEVELOPMENTAL NICOTINE EXPOSURE |
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| Authors/Affiliations: | 1 Naguib Mechawar*; 1 Maria Antonietta Davoli;
1 Douglas Institute, McGill University, Montreal, QC, Canada
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| Content: | Objectives: With the well-established risks of smoking during pregnancy, an increasing number of women are resorting to non-prescription nicotine replacement therapy (NRT) during childbearing. However, the short- and long-term consequences of NRT on brain and behavior in the offspring have not been explored. The main objective of the present study is to establish a rodent model of NRT exposure during brain development, and to examine the impact of such exposure on adult hippocampal neurogenesis, a phenomenon know to be (1) regulated in vivo by nicotinic pathways, (2) sensitive to early drug exposure, and (3) involved in various hippocampus-dependent cognitive functions.
Material and Methods: At gestational day 13, pregnant Sprague-Dawley rats were implanted with sub-cutaneous osmotic mini-pumps delivering either nicotine (1 mg/kg/d) or saline at a constant rate for the following four weeks. The offspring were thus exposed to these solutions in utero, during late embryogenesis, and then through breastfeeding until weaning at post-natal day 21. At three months of age, rats were injected with the cell proliferation marker BrdU (3 x 50 mg/kg i.p., 2h apart) and sacrificed 15 days later. Survival of newborn cells was evaluated by counting BrdU-immunolabeled profiles in the dentate gyrus (DG) of the hippocampus. Cell proliferation was determined from adjacent sections by counting ki-67-immunolabeled cells in the same region.
Results: Our preliminary results show that adult animals having been exposed to nicotine during early development have a slight (13%) but non-significant increase in DG cell proliferation compared to controls. In the same animals, however, the survival of newborn cells was greatly increased (47%; p<0.005) following early nicotine exposure. We are currently determining whether this increase reflects a change in hippocampal neurogenesis, and if this phenomenon has a behavioural consequence in the offspring.
Conclusion: These data are the first to suggest that early exposure to NRT-relevant doses of nicotine has a long-lasting influence on hippocampal neurogenesis.
Supported by a Douglas Mental Health University Institute start-up grant to NM
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