Abstract:
:Maternal cigarette use during pregnancy is associated with increased incidence of neural impairments in offspring, but nicotine's unique contribution to any neuropathology remains unclear, and nicotine's neurodevelopmental effects assessed in animal models vary with concentration. During ontogenesis, the chick oculomotor complex (OMN) is regulated by central nervous system (CNS) afferent-derived and target-derived trophic factors, allowing assessment of nicotine's potential interference in receptor-mediated CNS trophic phenomena, unconfounded by myriad other compounds in cigarette smoke. In the current study, 100 ng nicotine applied daily in ovo to yolk during embryonic days (E) 1-7 mimicked maternal plasma nicotine concentrations during fetal cranial nerve development. Nicotine-treated embryos exhibited a 15% decrease in whole body weight and 7% decrease in brain weight at E16. However, at E16, nicotine-treated embryos had 37% and 15% increases in the combined ventromedial+lateral (v) OMN motoneuron density and soma area, respectively, effects not observed in the optic tectum, in which nicotine cholinergic receptor expression is delayed until E8-12. Incorporation of tritiated thymidine into whole brain DNA demonstrated that the nicotine treatment did not cause increased rates of whole brain mitosis, suggesting that the dosage regimen did not elicit a cytotoxic, wound-healing, response of differentiating cells. As determined by DNA fragment-labeling assay during the normal period of cell death, vOMN apoptosis occurs maximally on E11 during a normal period of declining cell density, and a dose-response study demonstrated 78% E11 vOMN apoptotic suppression at approximately 0.30 microM cumulative yolk nicotine with an inhibition threshold between 0.10 and 0.20 microM. These results suggest that plasma nicotine concentrations resulting from tobacco use or nicotine replacement therapy (NRT) are sufficient to inhibit motoneuron apoptosis and enhance neuronal growth.
journal_name
Brain Resjournal_title
Brain researchauthors
Wielgus JJ,Corbin Downey L,Ewald KW,Hatley ME,Wilson KC,Yeilding RHdoi
10.1016/j.brainres.2003.11.070subject
Has Abstractpub_date
2004-03-12 00:00:00pages
123-33issue
1-2eissn
0006-8993issn
1872-6240pii
S000689930400054Xjournal_volume
1000pub_type
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