Hi-tech microscopy study gives clues about MND mechanisms

microscope images of cells

March 2022: Euan MacDonald Centre researchers have published findings indicating that a specialised connection between cells - the tripartite synapse - may play a key role in MND.

Many scientists around the world use high-powered microscopes to study MND in brain cells, and the Euan MacDonald Centre is no exception. The aim is to understand what happens in the cells of people with MND, compared with healthy controls, to try to uncover what causes motor neurons to degenerate in MND.

In this research, scientists from the Universities of St Andrews and Edinburgh collaborated to investigate the connections between brain cells, called synapses. The researchers pulled together two lines of evidence from previous studies: firstly that loss of synapses has been implicated as one of the earliest changes in cells in MND; and secondly that brain cells called astrocytes might be involved in MND. Astrocytes play a supporting role in the brain, helping the nerve cells grow and function properly.

Using these two lines of evidence, the researchers investigated the specialist types of connections made by astrocytes - so called 'tripartite synapses'. They studied millions of tripartite synapses using hi-tech microscopy techniques, visualising both human brain and spinal cord tissue, generously donated post-mortem by people with MND, and mouse brain and spinal cord tissue.

Interestingly, the researchers identified a loss of tripartite synapses in both human and mouse MND tissue that was not identified in healhy controls. Moreover, the astrocyte-associated tripartite synapses appeared to be more vulnerable to degeneration than were other synapse types.

These findings add another piece of information to the huge puzzle of what causes nerve cells to degenerate in MND. If the mechanisms of degeneration are understood, scientists can work to identify ways to stop or reverse these processes.

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Read the scientific article: Broadhead, M.J., Bonthron, C., Waddington, J. et al. Selective vulnerability of tripartite synapses in amyotrophic lateral sclerosis. Acta Neuropathol 143, 471–486 (2022). https://doi.org/10.1007/s00401-022-02412-9

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This article was published on: Sunday, March 20, 2022