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Impact of nicotinic signaling on neuronal gene expression

Institution: University of California, San Diego
Investigator(s): Karen Chang, BA
Award Cycle: 2000 (Cycle 9) Grant #: 9DT-0147 Award: $30,055
Subject Area: Nicotine Dependence
Award Type: Dissertation Awards
Abstracts

Initial Award Abstract
Tobacco smoking is the leading preventable cause of death and disease in the United States. Nicotine present in tobacco has been identified as the primary component driving its continued use despite harmful effects, but the mechanism behind nicotine abuse is not well understood. Nicotine exerts its effects in the body by acting on a family of proteins called nicotinic receptors that are responsible for relaying signals. These receptors are present on neurons and are activated by chemicals normally found in the body, namely acetylcholine. Acetylcholine can bind to and open nicotinic receptors, thereby allowing ions, including calcium, to flow into the neurons. This influx of ions can generate currents to further relay information electrically; the flow of calcium may be important for many cellular processes, such as producing changes in gene output. When these nicotinic receptors are inappropriately activated or blocked, neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia may result. Thus, nicotinic receptors are potentially important for normal brain function.

The experiments proposed here will allow us to better understand the role of nicotinic receptors in calcium-induced changes in gene expression and the pathways involved in information transfer. We will examine the ability of nicotine to change the activity of a factor important for gene expression, as well as identify the individual genes that have altered expression following nicotine treatment. In addition, experiments will be performed to correlate the extent of receptor activity to the degree of changes in gene expression. Since many aspects of nicotine and drug abuse have been related to changes in gene products within brain cells, the information obtained from these studies will allow us to gain insights into the mechanisms behind nicotine addiction and toxicity.
Publications

Synaptically driven calcium transients via nicotinic receptors on somatic spines
Periodical: Journal of Neuroscience Index Medicus:
Authors: Shoop RD, Chang KT, Ellisman MH, Berg DK ART
Yr: 2001 Vol: 21 Nbr: 3 Abs: Pg: 771-781

Neuronal gene regulation by synapticlly driven nicotinic receptors
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Chang KT, Berg DK ABS
Yr: 0 Vol: Nbr: Abs: Pg: