Summary of project PR000188

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000188. The data can be accessed directly via it's Project DOI: 10.21228/M8ZK5B This work is supported by NIH grant, U2C- DK119886.


Project ID: PR000188
Project DOI:doi: 10.21228/M8ZK5B
Project Title:Nicotine alters brain oxidative metabolism
Project Type:Pilot
Project Summary:Nicotine addiction through the use of cigarettes is the most common form of chemical dependency in the United States. Despite global warnings and awareness of the detrimental effects of smoking on health, smoking-derived nicotine dependence makes it very difficult to relinquish the habit. Unfortunately, nicotine exposure makes females more susceptible to ischemic neurodegeneration. Moreover, this susceptibility is enhanced when combined with oral contraceptives. Usually, women initiate nicotine usage during their adolescence, the period of life when one also is likely to get sexually active and also likely to use oral contraceptives. The underlying mechanisms responsible for the exacerbated neurodegeneration due to the long exposure of nicotine and oral contraceptives are not known. Our published studies showed that nicotine toxicity is exacerbated by oral contraceptives via altered mitochondrial function and increased reactive oxygen species production in the hippocampus of female rats. This mitochondrial dysfunction involved a defect on the enzymatic activity of the terminal enzyme of the electron transport chain (complex IV) as a consequence of an impaired biogenesis. However, how this mitochondrial impairment impacts the overall brain metabolism remains to be investigated. To understand the overall effect of nicotine on the brain metabolism and the mechanisms responsible for the enhanced toxicity of nicotine when combined with oral contraceptives, we propose two specific aims. We will investigate the metabolomic profile of brains (hippocampus) of female rats treated with nicotine alone or in combination with oral contraceptives. We will also determine the effect on the activity and steady-state levels of key regulatory metabolic enzymes. We will use an established rat animal model mimicking conditions of nicotine exposure produced by cigarette smoking and simulating conditions of oral contraceptives usage taking in consideration hormonal cycles in women. Discerning the exact effects of nicotine and its combination with oral contraceptives on overall brain metabolisms at different ages will open a new window for future therapeutic intervention. This intervention will reduce their susceptibility to neurodegenerative conditions in women trying to give up nicotine addiction.
Institute:University of Miami
Last Name:Raval
First Name:Ami
Address:1420 Nw, 9th Ave, Miami, FL -33136
Funding Source:AHA

Summary of all studies in project PR000188

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST000235 Sprague Dawley rats Nicotine alters brain oxidative metabolism Rattus norvegicus University of Florida MS* 2016-09-23 1 32 Uploaded data (3.7G)*