Acute and chronic synaptic pathology in multiple sclerosis gray matter.

Area of Science:

• Neuroscience
• Neuropathology

Background:

• Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
• Gray matter (GM) pathology, including inflammation and demyelination, significantly contributes to MS progression and disability.

Purpose of the Study:

• To quantify synaptic loss in multiple sclerosis (MS) brain tissue.
• To determine the role of gray matter (GM) inflammation and demyelination in synaptic loss.
• To differentiate synaptic changes in active versus chronic MS lesions and non-lesional GM.

Main Methods:

• Analysis of post-mortem brain tissue from MS patients and controls.
• Confocal microscopy used to identify and count over 1,000,000 synapses.
• Characterization of synapses as glutamatergic or GABAergic, correlated with neuronal/axonal loss.

Main Results:

• Significant synaptic loss (-58.9%) observed in active demyelinating GM lesions.
• Mild synaptic reduction (-12.6%) in chronic inactive GM lesions.
• Widespread synaptic loss (-21.2%) found in non-lesional GM of MS brains compared to controls.

Conclusions:

• Acute synaptic damage occurs during active inflammatory demyelination in MS.
• Synaptic reorganization is evident in chronically demyelinated GM.
• Synaptic loss in MS is widespread, affecting both lesional and non-lesional GM, and impacts glutamatergic and GABAergic synapses equally.