Acute and chronic synaptic pathology in multiple sclerosis gray matter

Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue. Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM...

Full description

Saved in:
Bibliographic Details
Published in:Multiple sclerosis 2022-03, Vol.28 (3), p.369-382
Main Authors: Vercellino, Marco, Marasciulo, Stella, Grifoni, Silvia, Vallino-Costassa, Elena, Bosa, Chiara, Pasanisi, Maria Barbara, Crociara, Paola, Casalone, Cristina, Chiò, Adriano, Giordana, Maria Teresa, Corona, Cristiano, Cavalla, Paola
Format: Article
Language:English
Subjects:
Autopsy
Brain
Brain - pathology
Confocal microscopy
Demyelination
Glutamatergic transmission
Gray Matter - pathology
Humans
Inflammation
Lesions
Multiple sclerosis
Multiple Sclerosis - pathology
Neurons - pathology
Substantia grisea
Synapses - pathology
Synaptic density
White Matter - pathology
γ-Aminobutyric acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue. Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM and cortical GM. MS brain samples had been specifically selected for the presence of active demyelinating GM lesions. Over 1,000,000 individual synapses were identified and counted using confocal microscopy, and further characterized as glutamatergic/GABAergic. Synaptic counts were also correlated with neuronal/axonal loss. Results: Important synaptic loss was observed in active demyelinating GM lesions (−58.9%), while in chronic inactive GM lesions, synaptic density was only mildly reduced compared to adjacent non-lesional gray matter (NLGM) (−12.6%). Synaptic loss equally affected glutamatergic and GABAergic synapses. Diffuse synaptic loss was observed in MS NLGM compared to control GM (−21.2% overall). Conclusion: This study provides evidence, in MS brain tissue, of acute synaptic damage/loss during active GM inflammatory demyelination and of synaptic reorganization in chronically demyelinated GM, affecting equally glutamatergic and GABAergic synapses. Furthermore, this study provides a strong indication of widespread synaptic loss in MS NLGM also independently from focal GM demyelination.
ISSN:1352-4585
1477-0970
DOI:10.1177/13524585211022174