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Selective vulnerability of inhibitory networks in multiple sclerosis
Lida Zoupi1, Sam A Booker2,3,4, Dimitri Eigel5
1Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, EH16 4UU, UK.
Acta Neuropathologica
|January 15, 2021
Summary
Multiple sclerosis (MS) causes neurodegeneration, particularly affecting inhibitory interneurons. A new rodent model of demyelination replicates this selective neuronal damage, offering a tool for developing neuroprotective treatments.
Area of Science:
- Neuroscience
- Neuropathology
- Demyelinating Diseases
Background:
- Multiple sclerosis (MS) is a chronic central nervous system demyelinating disease.
- Early neurodegeneration in MS correlates with long-term patient disability.
- The precise causes of MS-related neurodegeneration remain unclear, hindering treatment development.
Purpose of the Study:
- To investigate if MS-related neurodegeneration selectively impacts specific neuronal components.
- To determine if demyelination is the cause of selective neurodegeneration in MS.
Main Methods:
- Neuropathological examination of post-mortem motor cortex tissue from secondary progressive MS patients.
- Development and utilization of a rodent model of focal subpial cortical demyelination.
Main Results:
- A selective vulnerability of inhibitory interneurons was identified in the motor cortices of MS patients.
- The developed rodent model successfully replicated this selective neurodegeneration.
Conclusions:
- Inhibitory interneurons are selectively vulnerable in multiple sclerosis.
- The new rodent model provides a preclinical platform for evaluating neuroprotective strategies against MS-related neurodegeneration.
