Metabolic resilience of neuronal activity in a mouse model of Rett Syndrome

University of Glasgow

Past award

Daphne Jackson Fellow: Dr Elaine Hunter

Year Award Started: 2014

Rett syndrome (RTT) is a leading cause of severe disability in girls affecting 1 in 10,000 female births. >95% of girls with RTT have a mutation in the DNA of one gene, methyl-CpG-binding protein 2 (MeCP2), and mouse models have been developed to study this disease. MeCP2 mutations reduce a cell’s ability to make proteins; particularly those proteins involved in energy production within the mitochondria. This study will investigate whether mutations in MeCP2 cause a functional change in the ability of mitochondria to make energy in normal and RTT animals by measuring the amount of oxygen consumed by isolated mitochondria. In the brain, nerve cells which release the neurotransmitter GABA are the main system which calms electrical activity and regulates breathing rhythms. These GABAergic neurons are very active and have high energy demands. We will compare the electrical and mitochondrial activity of individual GABAergic neurons in RTT, to investigate whether their higher energy demands make them more sensitive to MECP2 mutation. This could provide a common cellular pathway linking the various neurological symptoms seen in RTT and open up a series of novel targets for drug development for the symptomatic treatment of the disorder.

Research area: Neurological conditions (including stroke)


Dr Stuart Cobb
Institute of Neuroscience and Psychology