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How do nic and cig smoke affect neural control of breathing?

Institution: University of California, Los Angeles
Investigator(s): Xuesi Shao, M.D.
Award Cycle: 2004 (Cycle 13) Grant #: 13RT-0164 Award: $392,620
Subject Area: Pulmonary Disease
Award Type: Research Project Awards

Initial Award Abstract
Breathing is a behavior driven and controlled by the central nervous system. Smoking has been associated with some prevalent disorders of respiratory control such as sudden infant death syndrome (SIDS) and sleep-disordered breathing (sleep apnea). SIDS is the second-ranking cause of infant death between one month and one year of age. Impaired control of breathing and arousal responsiveness are believed to be the underlying mechanisms. The incidence of SIDS is known to correlate to maternal smoking, but how it causes SIDS is unknown. About 6 to 7 percent of the U. S. population has sleep apnea, i.e., frequent episodes (up to several hundred per night) of limited or no ventilation during sleep. The public health burden attributable to sleep apnea is substantial because it causes high blood pressure and other cardiovascular disease, memory problems and lack of sleep leading to job impairment and a large number of (fatal) motor vehicle crashes.

Nicotine from cigarette smoke acts on nicotinic acetylcholine receptors in the brain affecting respiratory pattern. The long-term goal of this project is to understand the cellular mechanisms regarding how nicotine/cigarette smoke exposure contributes to pathogenesis of SIDS and sleep apnea. The objective of this application is to understand cellular and synaptic mechanisms underlying modulation of breathing by nicotine. Respiratory rhythm is believed to be generated in the brainstem. We have identified functional nicotinic receptors that modulate the neuronal function and neurotransmission, therefore affect breathing. We will determine how nicotine affects the central control of breathing and how activation of nicotinic receptors modulates excitatory amino acid neurotransmitter system and w will also determine the molecular compositions of nicotinic receptors involved in respiratory regulation. Insight into these cellular processes and the causes of the tobacco-related diseases such as SIDS and sleep apnea will provide a rational basis for prevention, diagnosis and treatment of these disorders as well as respiratory failure during organophosphate poisoning including nerve gases. Establishing the pre- or postsynaptic mechanisms of cholinergic modulation of breathing will lead to more effective treatments and will help also in the design of drugs more specific to target receptors with fewer side effects.

Miro-Agar salt bridge in patch -clamp electrode holder stabilizes electrode potentials
Periodical: Neuroscience Methods Index Medicus:
Authors: Shao XM and Feldman JL. ART
Yr: 2007 Vol: 159 Nbr: Abs: Pg: 108-115

Efficient measurement of endogenous neurotransmitter in small localized regions of central nervous system in vitro with HPLC
Periodical: Neuroscience Methods Index Medicus:
Authors: Shao XM and Feldman JL. ART
Yr: 2007 Vol: 160 Nbr: Abs: Pg: 256-263

Nicotinic receptors in preBĂ–tzinger Complex mediate cholinergic/nicotinic modulation of respiratory rhythm.
Periodical: Journal of Neuroscience Research Index Medicus:
Authors: Shao, XM, Tan, W, Xiu, J, Puskar, N, Fonck, C, Lester, HA, Feldman, JL. a4* ART
Yr: 0 Vol: 28 Nbr: Abs: Pg: 519 -528

Nicotinic receptors in the preBotzinger Complex that mediate modulation of respiratory patterncontain a4 subunits. Program No 424.8 2004 Society for Neuroscience Mtg. San Diego, CA
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Shao, XM, Labarca, C, Lester, HA, Feldman, JL ABS
Yr: 0 Vol: Nbr: 424.8 Abs: Pg:

Micro-agar salt bridge in patch-clamp electrode holder stabilizes electrode potentials. Socienty for Neuroscience Meeting, Atlanta, GA 2006 Online.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Shao, XM, Feldman, JL ABS
Yr: 0 Vol: Nbr: 200.17 Abs: Pg: