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SHS enhances cough via plasticity of brainstem neurons

Institution: University of California, Davis
Investigator(s): Jesse Joad, M.D.
Award Cycle: 2004 (Cycle 13) Grant #: 13RT-0004 Award: $387,150
Subject Area: Pulmonary Disease
Award Type: Research Project Awards

Initial Award Abstract
Children raised with exposure to second hand smoke experience more cough, wheeze, and phlegm production than children not exposed to second hand smoke. When exposed children catch a respiratory virus, they become sicker and need hospitalization more often. They have an earlier onset of asthma and more severe asthma. Some of these effects may be due to enhancement of the nerve reflexes that carry information from the lung to the brain with the end result of cough and narrowing of the airways. We have previously shown a number of changes in this reflex after exposing young guinea pigs to second hand smoke for five weeks, which is the equivalent of human childhood. Recently we showed that this second hand smoke exposure caused young guinea pigs to cough more and have more airway narrowing. When we put a blocker of one of the neurotransmitters, substance P, into an area of the brain that receives information from the lung, we were able to prevent the increase in cough and airway narrowing due to second hand smoke exposure. Our preliminary information shows that another neurotransmitter (gamma-aminobutyric acid, GABA) may also be changed by second hand smoke exposure. In this proposal we hypothesize that second hand smoke exposure increases substance P in this area of the brain which then inhibits the release of GABA. Since our preliminary experiments show that GABA inhibits cough and airway narrowing, the more the substance P, the less the inhibition of cough and airway narrowing by GABA. In our experiments we will expose the guinea pigs to filtered air or to second hand smoke from one week of age to six weeks of age. In our first set of experiments, we will cause the guinea pigs to cough and have airway narrowing with citric acid aerosol while we put various chemicals in the brain to inhibit substance P and GABA. In our next set of experiments, we will remove the brains of the guinea pigs and study how the nerve cells have been changed by the second hand smoke. This will involve measuring the electrical activity of the nerve cells in the presence of chemicals that inhibit substance P and GABA. Our final set of experiments will determine if the extra substance P produced by second hand smoke exposure comes from the nerves that go between the lung and the brain. These studies will examine the relationship between second hand smoke exposure and respiratory symptoms of young children. The studies may help determine whether drugs which affect GABA or substance P neurotransmission might help treat respiratory symptoms in children exposed to second hand smoke.

Air pollutants and cough.
Periodical: Pulmonary Pharmacology & Therapeutics Index Medicus:
Authors: Joad JP ART
Yr: 2007 Vol: 20 Nbr: Abs: Pg: 347-354

Down in the dumps, up in smoke: Pathways and dispartities in the relation between teen depressive ness and smoking
Periodical: American Association for Cancer Research Index Medicus:
Authors: Mistry R ABS
Yr: 2007 Vol: Nbr: Abs: Pg: