Numerous neurological disorders as well as advanced age are associated with declines in balance and motor co-ordination. Obtaining a better understanding of what underlies the decline in motor performance is essential to help develop interventions to improve the physical wellbeing of individuals afflicted with debilitating diseases and the expanding elderly population.
The cerebellum is the part of the brain central to maintaining balance and coordinated movement. The nerve cells critical for normal function of the cerebellum are Purkinje cells and when changes occur to these, the cerebellum no longer functions correctly, resulting in motor decline. First the Purkinje cells do not function properly, before beginning to degenerate and eventually die. This progression of events results in an escalating clinical decline, manifest firstly as difficulty in writing and eventually the need for a walking aid or a wheelchair.
We have found that loss of a protein (GLAST) from Bergmann glia, cells essential in supporting Purkinje cells, is directly involved in this disease progression. This project, employing pre-existing genetically modified mice and various molecular, biochemical and imaging techniques, aims to identify key signalling mechanisms critical for maintaining high levels of GLAST at the cell surface. GLAST is important in the removal of glutamate, a chemical essential for normal brain activity, but which, when present in high amounts, can be toxic. Therefore, insufficient GLAST protein causes glutamate accumulation, resulting in over-activation of Purkinje cells, leading to their demise. This project aims to identify mechanisms to prevent GLAST depletion and abnormal function of Bergmann glia, providing future targets for the development of interventions to alleviate progressive motor decline.
Dr Mandy Jackson
Dr Paul Skehel