Acute and chronic synaptic pathology in multiple sclerosis gray matter. (March 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Multiple sclerosis. Volume 28:Number 3(2022)
• Page Start: 369
• Page End: 382
• Publication Date: 2022-03
• Subjects: Multiple sclerosis -- synapse -- gray matter -- glutamate -- demyelination -- progressive; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/13524585211022174
• Languages: English
• ISSNs: 1352-4585

Abstract

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.