title: 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.
authors.affiliation: Department of Pharmacology & Cancer Biology; t.slotkin@duke.edu.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
authors.affiliation: Department of Pharmacology & Cancer Biology.
authors.forename: Ashley
authors.initials: A
authors.lastname: Stadler
authors.affiliation: Department of Pharmacology & Cancer Biology.
authors.forename: Samantha
authors.initials: S
authors.lastname: Skavicus
authors.affiliation: Department of Pharmacology & Cancer Biology.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Card
authors.affiliation: Department of Pharmacology & Cancer Biology.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ruff
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.affiliation: Department of Pharmacology & Cancer Biology.
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Seidler
mesh_terms: D000818:Animals; D005260:Female; D009420:Nervous System / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D011985:Receptors, Serotonin; D012906:Smoke
keywords: acetylcholine; developmental neurotoxicity; nicotine; serotonin: tobacco smoke.