MS Speaks

If I read this right, loss of synapses can occur in MS, but synaptic abnormalities can be reversed, and so they might be a possible avenue for development of therapies for MS.

From PubMed, November 21, 2015:

Nat Rev Neurol. 2015 Nov 20.

Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis

Mandolesi G1, Gentile A2, Musella A1, Fresegna D1, De Vito F2, Bullitta S1, Sepman H1,2, Marfia GA2, Centonze D3.

Author information

1IRCCS Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
2Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
3IRCCS Instituto Neurologico Mediterraneo (INM) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy.

Multiple sclerosis (MS) has long been regarded as a chronic inflammatory disease of the white matter that leads to demyelination and eventually to neurodegeneration.

In the past decade, several aspects of MS pathogenesis have been challenged, and degenerative changes of the grey matter, which are independent of demyelination, have become a topic of interest.

CNS inflammation in MS and experimental autoimmune encephalomyelitis (EAE; a disease model used to study MS in rodents) causes a marked imbalance between GABAergic and glutamatergic transmission, and a loss of synapses, all of which leads to a diffuse 'synaptopathy'.

Altered synaptic transmission can occur early in MS and EAE, independently of demyelination and axonal loss, and subsequently causes excitotoxic damage.

Inflammation-driven synaptic abnormalities are emerging as a prominent pathogenic mechanism in MS-importantly, they are potentially reversible and, therefore, represent attractive therapeutic targets.

In this Review, we focus on the connection between inflammation and synaptopathy in MS and EAE, which sheds light not only on the pathophysiology of MS but also on that of primary neurodegenerative disorders in which inflammatory processes contribute to disease progression.

PMID: 26585978

The abstract can be seen here.