In collaboration with researchers at Edinburgh University, work funded partly by MND Scotland, they have discovered that a specific type of brain cell called ‘microglia’ can become overactive in neurodegenerative diseases and destroy the small points of contact between brain cells, called synapses.
Microglia cells in the brain are intended to help maintain synapses, which transmit signals quickly and effectively through the neurons in the brain. But researchers have discovered that, in MND, these cells are actually damaging the synapses.
We already know that synapse loss is an early feature in MND, but as yet we have not known what causes this loss. Researchers believe that these findings may shed some light on this.
The team in Zurich used a new mouse model, in which a known MND-associated gene called TDP-43, was removed only in microglial cells. Surprisingly, the absence of this TDP-43 gene caused the microglia to become overactive and destroy synapses.
In Edinburgh, the team then examined donated brain tissue from MND patients and discovered that people who had changes in their TDP-43 protein also had lots of overactive microglia in their brain.
This finding in the human brain appears to match the result from the mouse model, namely that overactive microglia most likely play an important role in the disease.
This is an important finding because researchers may now be able to target microglia cells with drugs in the future, to prevent or even slow down their effects on the synapses and possibly preserve brain function.
Chris Henstridge | University of Edinburgh