In the Edwards lab, we are interested in how synapses change and how they react to each other in both health and disease.
1. How synapses work and change in the healthy brain: In healthy mouse brains we use high resolution recording techniques to measure the electrical communication between brain cells in acute brain slices. In addition, we can image these cells in detail and observe the changes that occur as connections strengthen and weaken both in response to incoming activity but also in response to changes in neighbouring connections. Understanding such subtle mechanisms is essential to understanding how the healthy network develops and is maintained in terms of general day-to-day function and the laying down and retrieval of memory. It is also these functions which are likely to go wrong in many neurodegenerative diseases.
2. What goes wrong in Alzheimer's disease: So far there has been no success in treating Alzheimer's disease. Although some drugs temporarily help the symptoms in some people, nothing has been discovered to slow or reverse the progression of the disease. Considering the massive scale of this disease and the devastating effects on the sufferers as well as their families, not to mention the economy, this is an urgent problem to address. Working on the hypothesis that the past failure is because the attempts at treatment come too late, once the brain is already too damaged for repair, we are both studying the earliest changes that occur and the middle period; a long window of opportunity as plaques develop but irreversible damage is yet to occur.
Using mice which express human genes with mutations known to occur in Alzheimer's disease and other disease states, we have observed substantial changes in synaptic transmission at very early stages. By understanding these changes we aim to develop new therapies in an attempt to stop the progression of the disease before substantial irreversible damage has occurred.
The work has now expanded to investigate the genome-wide gene expression in these mice revealing initial changes in synaptic genes followed by a very tight correlation between plaque development and immune genes. Later loss of synaptic genes, presumably indicated to loss of synapses and neurodegeneration is more closely linked to neurofibrillary tangles. Ongoing studies involve the manipulation of the genes of interest to understand which genes influence the susceptibility of the brain to the formation of neurofibrillary tangles and neurodegeneration.
GeoMx regional gene expression analysis
Protein assay, Western Blot
Organotypic 3D cultures from mice brain slices
Primary cell culture
Isolated microglial cultures