Research Awards
Jerry Yu, Ph.D.
University of Louisville
"Pulmonary Reflexes in Rett Syndrome"
2-Year Award: $100,000
Research Sponsor: Robert C. & Adele R. Schiff Foundation
Final Report (November 2005)
Supported by the Foundation, we have made significant progress in testing the hypothesis that one or more types of airway sensory receptors may be defective in Rett Syndrome patients and this defect may account for the abnormal breathing pattern. To achieve the goal, we first established techniques for assessing single unit activities in four different types of airway receptors [slowly adapting receptors (SARs), rapidly adapting receptors, C-fiber receptors, and high threshold A delta fiber receptors]. We also established a way to assess airway reflex sensitivity, including the Hering-Breuer reflex and the pulmonary chemoreflex. Except for SARs, no other airway sensory receptor has been recorded in mice. Thus, establishment of this technique was essential for the investigation of whether airway receptors are defective in RTT mice. Our studies demonstrate that mice possess all four types of airway sensors and reflex effects similar to those described in larger species. Our preliminary data also indicate that strength of the Hering-Breuer reflex is reduced in spontaneous breathing RTT mice. In anesthetized, open chest, mechanically ventilated mice, we recorded single unit activity from the SARs at different levels of constant pressure lung inflation, and showed that the receptor stimulus response curve (SARs activity plotted against airway pressure) shifted to the right in RTT mice. In addition, many SARs in RTT mice were inactive at the airway inflation pressure of 10 cm H2O, contrasting with SARs in normal mice, which were all active at a pressure of 10 cm H2O. Clearly, there is an increase in activation threshold of SARs in the RTT mouse model, suggesting there is a functional defect in this receptor. Such receptor behavior explains the less effective Hering-Breuer reflex observed in spontaneously breathing mice. It also can account for the slow deep breathing pattern observed in anesthetized RTT mice.
Jerry Yu, Ph.D.University of Louisville
"Pulmonary Reflexes in Rett Syndrome"
2-Year Award: $100,000
Research Sponsor: Robert C. & Adele R. Schiff Foundation
Final Report (November 2005)
Supported by the Foundation, we have made significant progress in testing the hypothesis that one or more types of airway sensory receptors may be defective in Rett Syndrome patients and this defect may account for the abnormal breathing pattern. To achieve the goal, we first established techniques for assessing single unit activities in four different types of airway receptors [slowly adapting receptors (SARs), rapidly adapting receptors, C-fiber receptors, and high threshold A delta fiber receptors]. We also established a way to assess airway reflex sensitivity, including the Hering-Breuer reflex and the pulmonary chemoreflex. Except for SARs, no other airway sensory receptor has been recorded in mice. Thus, establishment of this technique was essential for the investigation of whether airway receptors are defective in RTT mice. Our studies demonstrate that mice possess all four types of airway sensors and reflex effects similar to those described in larger species. Our preliminary data also indicate that strength of the Hering-Breuer reflex is reduced in spontaneous breathing RTT mice. In anesthetized, open chest, mechanically ventilated mice, we recorded single unit activity from the SARs at different levels of constant pressure lung inflation, and showed that the receptor stimulus response curve (SARs activity plotted against airway pressure) shifted to the right in RTT mice. In addition, many SARs in RTT mice were inactive at the airway inflation pressure of 10 cm H2O, contrasting with SARs in normal mice, which were all active at a pressure of 10 cm H2O. Clearly, there is an increase in activation threshold of SARs in the RTT mouse model, suggesting there is a functional defect in this receptor. Such receptor behavior explains the less effective Hering-Breuer reflex observed in spontaneously breathing mice. It also can account for the slow deep breathing pattern observed in anesthetized RTT mice.