Synaptic plasticity and PDGF signaling defects underlie clinical progression in multiple sclerosis

Francesco Mori, Silvia Rossi, Sonia Piccinin, Caterina Motta, Dalila Mango, Hajime Kusayanagi, Alessandra Bergami, Valeria Studer, Carolina G. Nicoletti, Fabio Buttari, Francesca Barbieri, Nicola B. Mercuri, Gianvito Martino, Roberto Furlan, Robert Nisticò, Diego Centonze

Research output: Contribution to journalArticle

Abstract

Neuroplasticity is essential to prevent clinical worsening despite continuing neuronal loss in several brain diseases, including multiple sclerosis (MS). The precise nature of the adaptation mechanisms taking place in MS brains, ensuring protection from disability appearance and accumulation, is however unknown. Here, we explored the hypothesis that long-term synaptic potentiation (LTP), potentially able to minimize the effects of neuronal loss by providing extra excitation of denervated neurons, is the most relevant form of adaptive plasticity in stable MS patients, and it is disrupted in progressing MS patients. We found that LTP, explored by means of transcranial magnetic theta burst stimulation over the primary motor cortex, was still possible, and even favored, in stable relapsing-remitting (RR-MS) patients, whereas it was absent in individuals with primary progressive MS (PP-MS). We also provided evidence that plateletderived growth factor (PDGF) plays a substantial role in favoring both LTP and brain reserve in MS patients, as this molecule: (1) was reduced in the CSF of PP-MS patients, (2) enhanced LTP emergence in hippocampal mouse brain slices, (3) was associated with more pronounced LTP in RR-MS patients, and (4) was associated with the clinical compensation of new brain lesion formation in RR-MS. Our results show that brain plasticity reserve, in the form of LTP, is crucial to contrast clinical deterioration in MS. Enhancing PDGF signaling might represent a valuable treatment option to maintain brain reserve and to attenuate the clinical consequences of neuronal damage in the progressive phases of MS and in other neurodegenerative disorders.

Original languageEnglish
Pages (from-to)19112-19119
Number of pages8
JournalJournal of Neuroscience
Volume33
Issue number49
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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    Mori, F., Rossi, S., Piccinin, S., Motta, C., Mango, D., Kusayanagi, H., Bergami, A., Studer, V., Nicoletti, C. G., Buttari, F., Barbieri, F., Mercuri, N. B., Martino, G., Furlan, R., Nisticò, R., & Centonze, D. (2013). Synaptic plasticity and PDGF signaling defects underlie clinical progression in multiple sclerosis. Journal of Neuroscience, 33(49), 19112-19119. https://doi.org/10.1523/JNEUROSCI.2536-13.2013