Neuronal nicotinic acetylcholine receptors (neuronal nAChRs) are the physiological site of action in the brain for nicotine, the addictive substance naturally produced in tobacco. Tobacco use exposes a significant proportion of our population to nicotine, a molecule with demonstrated teratogenic actions, detrimental in vivo effects on cell proliferation, differentiation, and synaptic activity. This proposal outlines basic research on the actual physiological target of nicotine in the central nervous system (CNS), the neuronal nAChR. There are many possible subtypes of neuronal nAChRs, and their expression can be influenced by environmental exposure(s) to various compounds. Besides playing a central role in reinforcing tobacco addiction, other neuronal nAChRs have a role in coordinating hippocampal activity, and are thus involved in learning and memory. Recently, it has been demonstrated that B-amyloid protein (which accumulates in the CNS during Alzheimer?s disease) can bind to and interfere with signaling through neuronal nAChRs. The underlying causes for Alzheimer?s disease are currently unknown, however this disease is strongly correlated with a decrease in cholinergic neurotransmission. This study investigates how one of the hallmark occurrences associated with Alzheimer?s disease, B-amyloid secretion in the CNS, may promote dementia by interfering with synaptic transmission through neuronal nAChRs in the hippocampus. This proposal outlines an approach for characterizing the nAChR subtypes in the hippocampus using a combination of quantitative single-cell RT-PCR and patch-clamp electrophysiology techniques for determining the physiological effects of B-amyloid on these nAChR subtypes. By completing the research outlined in this proposal the investigators hope to gain significant insight into how environmental exposures can affect individual susceptibility to Alzheimer?s disease, and how they can better treat and/or prevent this severely debilitating disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Career Transition Award (K22)
Project #
1K22ES011639-01
Application #
6472448
Study Section
Special Emphasis Panel (ZES1-LKB-E (KT))
Program Officer
Shreffler, Carol K
Project Start
2002-09-30
Project End
2005-08-31
Budget Start
2002-09-30
Budget End
2003-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$105,336
Indirect Cost
Name
Brigham Young University
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
City
Provo
State
UT
Country
United States
Zip Code
84602