Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

Abstract

Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets.

Structural networks involved in attention and executive functions in multiple sclerosis

“…Functional MRI studies have found increased activity during PASAT performance in MS (Bonnet et al, 2010, Chiaravalloti et al, 2015, Ksiazek-Winiarek et al, 2015, Morgen et al, 2007, Rocca et al, 2016). Indeed, Morgen et al (2007) found that low PASAT scores correlated with reduction of activation of anterior cingulate cortex, but also with enlarged activation of frontoparietal regions and more widely distributed cortical recruitment as an effort to maintain cognitive functioning.…”

Altered motor plasticity in an acute relapse of multiple sclerosis

“…However, relapses of MS have been shown to be associated with inflammation affecting the whole CNS rather than being limited to one functional area. Relapse pathophysiology is dominated by T helper cells and secretion of a variety of proinflammatory mediators (Ciccarelli et al, 2014;Kalincik, 2015;Kallaur et al, 2016), some of which have been implicated in the modulation of synaptic plasticity (Mori et al, 2014b;Blakely et al, 2015;Ksiazek-Winiarek et al, 2015). In view of this association between generalized inflammation and plasticity within the CNS, we suggest that PAS may represent a measure of cortical plasticity in the group of patients with MS irrespective of the individual nature of their relapse.…”

The Changing Brain

“…Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder that results in motor and cognitive dysfunction. Inflammatory cells are known to infiltrate a variety of brain regions resulting in the modulation of regular neuronal function, synaptic signal formation, and brain plasticity (Ksiazek-Winiarek, Szpakowski, & Glabinski, 2015). In addition to repair mechanisms like remyelination, an important factor within disease progression lies in neuronal plasticity, whereby structural and functional reorganization occurs throughout the life history in MS patients.…”

“…In addition to repair mechanisms like remyelination, an important factor within disease progression lies in neuronal plasticity, whereby structural and functional reorganization occurs throughout the life history in MS patients. BDNF and CB1 receptor activity have been implicated as potential therapeutic targets in the functional recovery of acute phase MS (Ksiazek-Winiarek et al, 2015). CB1 is suggested to act as a regulator of glutamate transmission, acting as a buffer for excitotoxicity effects and helping to maintain LTP-like neuronal plasticity.…”