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

dc.contributor.author

Slotkin, Theodore A

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Stadler, Ashley

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Skavicus, Samantha

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Card, Jennifer

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Ruff, Jonathan

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Levin, Edward D

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Seidler, Frederic J

dc.date.accessioned

2024-01-01T15:48:43Z

dc.date.available

2024-01-01T15:48:43Z

dc.date.issued

2017-01

dc.description.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.

dc.identifier

kfw180

dc.identifier.issn

1096-6080

dc.identifier.issn

1096-0929

dc.identifier.uri

https://hdl.handle.net/10161/29583

dc.language

eng

dc.publisher

Oxford University Press (OUP)

dc.relation.ispartof

Toxicological sciences : an official journal of the Society of Toxicology

dc.relation.isversionof

10.1093/toxsci/kfw180

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Nervous System

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Animals

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Rats

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Tobacco

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Receptors, Serotonin

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Smoke

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Pregnancy

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Female

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

pubs.begin-page

75

pubs.end-page

84

pubs.issue

1

pubs.organisational-group

Duke

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Nicholas School of the Environment

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School of Medicine

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Trinity College of Arts & Sciences

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Neurobiology

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Pharmacology & Cancer Biology

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Psychiatry & Behavioral Sciences

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Duke Cancer Institute

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Psychology & Neuroscience

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Environmental Sciences and Policy

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Initiatives

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Duke Science & Society

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

pubs.publication-status

Published

pubs.volume

155

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