Reference:
Paton, Julian
Abstract:
Breathing abnormalities consisting of rapid deep respiration followed by cessation of breathing and an irregular interval between breaths are a common and distressing feature of Rett syndrome (RTT). Using a mouse model we have shown that injections of a compound that boosts the brain concentration of the inhibitory neurotransmitter ? amino-butyric acid (GABA) markedly reduces the incidence of these respiratory disturbances in heterozygous females. Drugs of this type are not available for children. We, however, also showed that an activator of serotonin at 1a receptors improves respiration to a similar degree. To date the treatments have involved all organs and tissues in the animals. In order to better understand the basis of the respiratory problems in RTT, this proposal will examine the effects of activating serotonin receptors in very localized areas of the brain so as to define the population of neurons that are causing the breathing problems. We will also establish that the serotonin activist works by enhancing a specific potassium ion channel. Establishing that serotonin acts by activation a specific type of potassium channel will pave the way for treatments that target these potassium channels directly. We will further strengthen our hypothesis by anatomical studies that count the number of connections that GABA neurons make with expiratory neurons. Taken together these studies may lead to new treatments for the respiratory disorders in Rett syndrome. – See more at: http://www.rettsyndrome.org/research-programs/funded-projects/research-awardees-2010#sthash.Nk5rINCS.dpuf
PROJECT DETAILS
beginning: 2010.
end: 2012.
Country of research: United Kingdom
Counry of funding source: United States
Funding organization: International Rett Syndrome Foundation (Regular Research Grant)
Financing: PRIVATE FUNDERS – 146 872 €