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Mechanisms of Nicotine-Induced Neurotoxicity in the Developing Brain

EPA Grant Number: U915463
Title: Mechanisms of Nicotine-Induced Neurotoxicity in the Developing Brain
Investigators: Trauth, Jennifer
Institution: Duke University
EPA Project Officer: Manty, Dale
Project Period: July 1, 1998 through January 1, 2001
Project Amount: $71,039
RFA: STAR Graduate Fellowships (1998)
Research Category: Fellowship - Toxicology , Health Effects , Academic Fellowships

Description:

Objective:

The objectives of this research project are to: (1) elucidate the mechanisms of nicotine-induced neurotoxicity in the context of central nervous system development; and (2) determine whether critical periods exist for these mechanisms.

Approach:

Rats are exposed to nicotine using two different paradigms that are based on exposure period. Prenatal exposure is achieved via implantation of an osmotic minipump in dams on gestational day 4, with exposure continuing until gestational day 21. Adolescent exposure, also via minipump implantation, extends from postnatal day 30 to 47. Several parameters are measured both during and up to several weeks following the exposure period in a variety of brain regions. The total cell number is determined by assaying DNA content, and the nicotinic receptor number is determined by a ligand-binding assay. The expression of various RNA transcripts is assessed using a slot-blotting technique. Synaptic function is assessed via neurotransmitter content, turnover, and release using high performance liquid chromatography and radioligand release. After the data have been gathered from biochemical and molecular assays, behavioral tests will be identified and conducted.

Supplemental Keywords:

fellowship, nicotine, brain development, neurotoxicity, central nervous system development. , Scientific Discipline, Health, RFA, Toxicology, Biology, Risk Assessments, Disease & Cumulative Effects, Chemistry, Children's Health, Genetics, gene expression, developmental disorders, toxicity, developmental effects, developmental toxicity, apoptosis, fetus, prenatal nicotine, cigarette smoke, prenatal exposure, exposure limits, neonates, nervous system function, Nicotine, tobacco smoke, modeling, environmental health hazard, model, animal model

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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