Linked Life Data

15316571

Source:http://linkedlifedata.com/resource/pubmed/id/15316571

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-20
pubmed:abstractText
Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers (30 ng/ml). Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage. Nicotine evoked nAChR upregulation, but with distinct regional disparities indicative of selective stimulatory responses. Similarly, indices of cell loss (reduced DNA), cell size and neuritic outgrowth (protein/DNA and membrane/total protein ratios) were distinct for each region and did not necessarily follow the rank order of nAChR upregulation, suggesting the involvement of additional mechanisms such as oxidative stress. We then attempted to offset the adverse effects of nicotine with standard dietary supplements known to interact with nicotine. By itself, choline elicited nicotine-like actions commensurate with its promotion of cholinergic neurotransmission. When given in combination with nicotine, choline protected some regions from damage but worsened nicotine's effects in other regions. Similarly, Vitamin C supplementation had mixed effects, increasing nAChR responses while providing protection from cell damage in the caudate, the brain region most susceptible to oxidative stress. Our results indicate that nicotine elicits neurodevelopmental damage that is highly selective for different brain regions, and that dietary supplements ordinarily thought to be neuroprotectant may actually worsen some of the adverse effects of nicotine on the fetal brain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0893-133X
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
129-44
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed-meshheading:15316571-Adenylate Cyclase, pubmed-meshheading:15316571-Animals, pubmed-meshheading:15316571-Antioxidants, pubmed-meshheading:15316571-Ascorbic Acid, pubmed-meshheading:15316571-Biological Markers, pubmed-meshheading:15316571-Brain, pubmed-meshheading:15316571-Choline, pubmed-meshheading:15316571-DNA, pubmed-meshheading:15316571-Female, pubmed-meshheading:15316571-Heart, pubmed-meshheading:15316571-Macaca mulatta, pubmed-meshheading:15316571-Nicotine, pubmed-meshheading:15316571-Nicotinic Agonists, pubmed-meshheading:15316571-Nootropic Agents, pubmed-meshheading:15316571-Oxidative Stress, pubmed-meshheading:15316571-Pregnancy, pubmed-meshheading:15316571-Prenatal Exposure Delayed Effects, pubmed-meshheading:15316571-Receptors, Neurotransmitter, pubmed-meshheading:15316571-Signal Transduction, pubmed-meshheading:15316571-Thiobarbituric Acid Reactive Substances
pubmed:year
2005
pubmed:articleTitle
Effects of prenatal nicotine exposure on primate brain development and attempted amelioration with supplemental choline or vitamin C: neurotransmitter receptors, cell signaling and cell development biomarkers in fetal brain regions of rhesus monkeys.
pubmed:affiliation
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. t.slotkin@duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't