Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?

Abstract

Secondhand tobacco smoke exposure in pregnancy increases the risk of neurodevelopmental disorders. We evaluated in rats whether there is a critical period during which tobacco smoke extract (TSE) affects the development of acetylcholine and serotonin systems, prominent targets for adverse effects of nicotine and tobacco smoke. We simulated secondhand smoke exposure by administering TSE so as to produce nicotine concentrations one-tenth those in active smoking, with 3 distinct, 10-day windows: premating, early gestation or late gestation. We conducted longitudinal evaluations in multiple brain regions, starting in early adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure in any of the 3 windows impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although the adverse effects were seen for all 3 treatment windows, there was a distinct progression, with lowest sensitivity for premating exposure and higher sensitivity for gestational exposures. Serotonin receptors were also reduced by TSE exposure with the same profile: little effect with premating exposure, intermediate effect with early gestational exposure and large effect with late gestational exposure. As serotonergic circuits can offset the neurobehavioral impact of cholinergic deficits, these receptor changes were maladaptive. Thus, there is no single 'critical period' for effects of low-level tobacco smoke but there is differential sensitivity dependent upon the developmental stage at the time of exposure. Our findings reinforce the need to avoid secondhand smoke exposure not only during pregnancy, but also in the period prior to conception, or generally for women of childbearing age.

Environmental Tobacco Smoke During the Early Postnatal Period of Mice Interferes With Brain 18 F-FDG Uptake From Infancy to Early Adulthood – A Longitudinal Study

“…These results are in accordance with previous studies of our group and with studies that show that exposure to tobacco smoke during brain development can affect the central nervous system. Exposure to tobacco smoke extract during gestational period of Sprague-Dawley rats decreased nicotinic and serotonin receptors in different brain regions (Slotkin et al, 2017). In addition, postnatal exposure to tobacco smoke leads to impairment in the myelination, learning, and memory, and induces oxidative stress and lower brain-derived neurotrophic factor (BDNF) and synaptic proteins levels (Stangherlin et al, 2009;Lobo-Torres et al, 2012;Torres et al, 2015a,b).…”

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

“…The capacity for early gestational exposure to an extract from tobacco smoke to alter neurodevelopmental outcomes was recently reported in a Sprague-Dawley rat model (Slotkin et al, 2016). In this study, pregnant dams were exposed to tobacco smoke extract by infusion minipumps for the first ten days of gestation, resulting in perturbations to both the cholinergic and serotonergic systems in the postnatal offspring (Slotkin et al, 2016).…”

“…In this study, pregnant dams were exposed to tobacco smoke extract by infusion minipumps for the first ten days of gestation, resulting in perturbations to both the cholinergic and serotonergic systems in the postnatal offspring (Slotkin et al, 2016).…”

Frontal Cortex Proteome Perturbation after Juvenile Rat Secondhand Smoke Exposure

“…Yet, the same group separately observed that ETS influenced synaptic organization within the hippocampus, an area with no direct cerebellar feedback [19] . Recently researchers at Duke reported that the PFC was vulnerable in utero to doses of ETS condensate, which they directly contrasted with nicotine alone [6,20] . They determined that ETS condensate was more bioactive than nicotine in driving synaptic abnormality in the PFC.…”