Selective brain cell loss in MS - a new focus in search for treatments

15 January 2021

A new study of human brain tissue from patients with multiple sclerosis (MS) has identified the selective loss of inhibitory brain cells, while those brain cells that stimulate brain activity are present in normal numbers. The discovery offers a new focus in the search for treatments for MS.

Brain cells come in two main types - those that stimulate responses (excitatory) and those that dampen responses (inhibitory). Until now, it was not known whether particular neurons were affected in MS. Post-mortem tissue samples from people with MS show a dramatic reduction in the number of inhibitory brain cells, or neurons. Inhibitory neurons act like a brake, reducing and controlling the activity of excitatory neurons.

MS is a disease of the brain and spinal cord where there is loss of the protective covering of nerves (myelin) and loss of the nerves themselves (neurodegeneration). So far treatments have focussed on the loss of myelin (demyelination). Around 2.5M people worldwide have MS, with Scotland having the highest number of MS cases per capita in the world. This study offers a new focus for researchers in the search for treatments of the disease.

The study team also saw the same pattern of inhibitory neuron loss in a new mouse model of demyelination in the cortex (the outer layer of the brain where brain cells are found), with very early loss of these neurons after demyelination.

The study was led by Professor Anna Williams of the University of Edinburgh Centre for Regenerative Medicine and MS Society Edinburgh Centre for MS Research. First author, Dr Lida Zoupi and colleagues looked at the numbers of different types of neurons in post-mortem brain tissue from MS patients who donated their brains for research to the MS Society UK Tissue Bank.

Dr Zoupi said, “The results of this study are important as it focusses our efforts on trying to stop damage and death of these special inhibitory nerve cells and their connections, and gives us an animal model with which to test new treatments.”

Professor Williams said, “Our next step is to find such treatments through work in the MS Society Edinburgh Centre for MS Research, using all of our tools to convert this new knowledge into treatments to prevent neurodegeneration in MS patients.”

Post-mortem brain tissue was provided by the Edinburgh Brain and Tissue Bank and the MS Society UK Tissue Bank.

The study has been published in the scientific journal Acta Neuropathologica and was primarily supported by funding from MS Society UK and the Medical Research Council. Additional funding is acknowledged  from the UK Dementia Research Institute which receives funding from Alzheimer’s Research UK, Alzheimer’s Research UK, the Alzheimer’s Society, the European Research Council (ERC), the Deutsche Forschungsgemeinschaft (DFG), the Simons Foundation Autism Research Initiative and the Patrick Wild Centre.

Acta Neuropatholgica article

Anna Williams Research Group

Microscope image of mouse brain showing loss of inhibitory neurones in a model of multiple sclerosis
Mouse brain cortex (where brain cells are found, with cell nuclei in blue) with an area of myelin loss (outlined with a white line) with myelin in green). Inhibitory neurons (red) are the brain cells that are mostly affected by the loss of myelin which makes them lose their connections and die in contrast to the excitatory brain cells.