Abstract
RationaleThe influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT) as a smoking cessation method during pregnancy.ObjectivesIn this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic lifelong phenomena in the dentate gyrus (DG) of the hippocampus that are highly sensitive to the environment: granule cell neurogenesis and long-term potentiation (LTP).MethodsPregnant rats were implanted with osmotic mini-pumps delivering either nicotine or saline solutions. Plasma nicotine and metabolite levels were measured in dams and offspring. Corticosterone levels, DG neurogenesis (cell proliferation, survival and differentiation) and glutamatergic electrophysiological activity were measured in pups.ResultsJuvenile (P15) and adolescent (P41) offspring exposed to nicotine throughout prenatal and postnatal development displayed no significant alteration in DG neurogenesis compared to control offspring. However, NRT-like nicotine exposure significantly increased LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices, suggesting that the mechanisms underlying nicotine-induced LTP enhancement previously described in adult rats are already functional in pups.ConclusionsThese results indicate that synaptic plasticity is disrupted in offspring breastfed by dams passively exposed to nicotine in an NRT-like fashion.
Highlights
It is estimated that 10–25% of women smoke tobacco during pregnancy [1,2]
We report that rats chronically exposed to NRTlike conditions during both prenatal and postnatal development do not display alterations in dentate gyrus (DG) neurogenesis but show significantly enhanced DG long-term potentiation (LTP) compared to saline-exposed controls
Average pup weight did not display any significant variation between saline- and nicotine-exposed pups at any age examined between postnatal day 2 (P2) and weaning (Fig. 1)
Summary
It is estimated that 10–25% of women smoke tobacco during pregnancy [1,2]. This addiction has well-documented adverse effects on pregnancies, as it is associated with increased occurrences of placenta previa, premature delivery and stillbirth, and is the main cause of low birth weight in Western societies [3]. Children born from mothers who smoke are more susceptible to sudden infant death syndrome (SIDS) [4] They have been reported to display cognitive deficits [5,6,7], and to run a greater risk of developing psychiatric conditions including anxiety disorders [8] and attention deficit hyperactivity disorder (ADHD) [9,10]. These studies highlight the vulnerability of developing brains to tobacco smoke that, in addition to the addictive compound nicotine, contains several other neuroactive molecules [11]. Longitudinal data on NRT safety during pregnancy and breastfeeding, and its possible influence on cognition and behavior in offspring, have yet to be produced
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