Growth factors and synaptic plasticity in relapsing-remitting multiple sclerosis

Francesco Mori, Carolina G. Nicoletti, Silvia Rossi, Caterina Motta, Hajime Kusayanagi, Alessandra Bergami, Valeria Studer, Fabio Buttari, Francesca Barbieri, Sagit Weiss, Robert Nisticò, Gianvito Martino, Roberto Furlan, Diego Centonze

Research output: Contribution to journalArticlepeer-review


During multiple sclerosis (MS) inflammatory attacks, and in subsequent clinical recovery phases, immune cells contribute to neuronal and oligodendroglial cell survival and tissue repair by secreting growth factors. Animal studies showed that growth factors also play a substantial role in regulating synaptic plasticity, and namely in long-term potentiation (LTP). LTP could drive clinical recovery in relapsing patients by restoring the excitability of denervated neurons. We recently reported that maintenance of synaptic plasticity reserve is crucial to contrast clinical deterioration in MS and that the platelet-derived growth factor (PDGF) may play a key role in its regulation. We also reported that a Hebbian form of LTP-like cortical plasticity, explored by paired associative stimulation (PAS), correlates with clinical recovery from a relapse in MS. Here, we explored the role of PDGF in clinical recovery and in adaptive neuroplasticity in relapsing-remitting MS (RR-MS) patients. We found a correlation between the cerebrospinal fluid (CSF) PDGF concentrations and the extent of clinical recovery after a relapse, as full recovery was more likely observed in patients with high PDGF concentrations and poor recovery in subjects with low PDGF levels. Consistently with the idea that PDGF-driven synaptic plasticity contributes to attenuate the clinical consequences of tissue damage in RR-MS, we also found a striking correlation between CSF levels of PDGF and the amplitude of LTP-like cortical plasticity explored by PAS. CSF levels of fibroblast growth factor, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor did not correlate with clinical recovery nor with measures of synaptic transmission and plasticity.

Original languageEnglish
Pages (from-to)490-498
Number of pages9
JournalNeuroMolecular Medicine
Issue number2
Publication statusPublished - 2014


  • CSF
  • PAS
  • PDGF
  • Recovery
  • Relapse
  • TMS

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology
  • Medicine(all)


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