Research Awards
Judith Neubauer, Ph.D.
University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School
"Cardiorespiratory Control in Rett Syndrome"
2-Year Award: $99,000
Research Sponsor: Schmidlapp Fund
Lay Progress Report (August, 2003)
RTT is associated with significant respiratory disturbances indicating that there is some inability of the respiratory centers in the brain "to stabilize" the breathing pattern. Breathing is usually a fairly rhythmic process and doesn't exhibit periods of rapid breathing followed by periods of reduced breathing as can occur in RTT. How the respiratory center stabilizes breathing normally and why it doesn't in RTT, is the focus of our research project funded by the RSRF. Our previous work has suggested that the stability of breathing may require the ability of the respiratory center to produce large breaths (sighs), which act to "reset" the pattern should it be deviating from the rhythmic pattern. Everyone generally sighs about six times an hour and this presumably is sufficient to keep the pattern at the desired set point. In addition, the number of sighs increases under conditions like hypoxia, since hypoxia may increase the tendency of the pattern to either overshoot or undershoot a set point. In order to determine if the impaired ability to stabilize breathing in RTT is linked with an inability to increase sighs, we have taken advantage of the Mecp2 knockout mouse to study the stability of breathing during conditions that would normally increase sighs. Our initial results have been very exciting. We have found that the Mecp2 knockout mouse does not have spontaneous sighs nor does it sigh even when exposed to hypoxia. One is always cautious when interpreting preliminary results, but if this observation can be confirmed with repeated experiments it may suggest potential strategies for treating respiratory disturbances in RTT. For example, we now know the part of the brain that is necessary to produce sighs, a part of the respiratory center called the pre-B^tzinger Complex. What is of particular interest, is that another RSRF funded investigator (Dr Ramirez) has shown that the pre-B^tzinger Complex in Mecp2 knockout mice is lacking the appropriate number of receptors for a substance called substance P, which may be essential for activation of this site to generate sighs. Taken together, this may lead to identification of drugs that could selective increase the ability of the pre-B^tzinger Complex to produce sighs and, thereby, stabilize the breathing pattern.
Judith Neubauer, Ph.D.University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School
"Cardiorespiratory Control in Rett Syndrome"
2-Year Award: $99,000
Research Sponsor: Schmidlapp Fund
Lay Progress Report (August, 2003)
RTT is associated with significant respiratory disturbances indicating that there is some inability of the respiratory centers in the brain "to stabilize" the breathing pattern. Breathing is usually a fairly rhythmic process and doesn't exhibit periods of rapid breathing followed by periods of reduced breathing as can occur in RTT. How the respiratory center stabilizes breathing normally and why it doesn't in RTT, is the focus of our research project funded by the RSRF. Our previous work has suggested that the stability of breathing may require the ability of the respiratory center to produce large breaths (sighs), which act to "reset" the pattern should it be deviating from the rhythmic pattern. Everyone generally sighs about six times an hour and this presumably is sufficient to keep the pattern at the desired set point. In addition, the number of sighs increases under conditions like hypoxia, since hypoxia may increase the tendency of the pattern to either overshoot or undershoot a set point. In order to determine if the impaired ability to stabilize breathing in RTT is linked with an inability to increase sighs, we have taken advantage of the Mecp2 knockout mouse to study the stability of breathing during conditions that would normally increase sighs. Our initial results have been very exciting. We have found that the Mecp2 knockout mouse does not have spontaneous sighs nor does it sigh even when exposed to hypoxia. One is always cautious when interpreting preliminary results, but if this observation can be confirmed with repeated experiments it may suggest potential strategies for treating respiratory disturbances in RTT. For example, we now know the part of the brain that is necessary to produce sighs, a part of the respiratory center called the pre-B^tzinger Complex. What is of particular interest, is that another RSRF funded investigator (Dr Ramirez) has shown that the pre-B^tzinger Complex in Mecp2 knockout mice is lacking the appropriate number of receptors for a substance called substance P, which may be essential for activation of this site to generate sighs. Taken together, this may lead to identification of drugs that could selective increase the ability of the pre-B^tzinger Complex to produce sighs and, thereby, stabilize the breathing pattern.