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Growth Factors and Synaptic Plasticity in Relapsing–Remitting Multiple Sclerosis

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Abstract

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.

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Acknowledgments

This study was supported by a Grant from Fondazione Italiana Sclerosi Multipla to DC (FISM Special Project 2012/S/2).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133, Rome, Italy

    Francesco Mori, Carolina G. Nicoletti, Silvia Rossi, Caterina Motta, Hajime Kusayanagi, Valeria Studer, Fabio Buttari, Francesca Barbieri, Sagit Weiss & Diego Centonze

  2. IRCCS Fondazione Santa Lucia, 00143, Rome, Italy

    Francesco Mori, Carolina G. Nicoletti, Silvia Rossi, Caterina Motta, Hajime Kusayanagi, Valeria Studer, Fabio Buttari, Francesca Barbieri, Sagit Weiss, Robert Nisticò & Diego Centonze

  3. Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, 20132, Milan, Italy

    Alessandra Bergami, Gianvito Martino & Roberto Furlan

  4. Dipartimento di Fisiologia e Farmacologia, Università La Sapienza, 00185, Rome, Italy

    Robert Nisticò

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  1. Francesco Mori
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  2. Carolina G. Nicoletti
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  3. Silvia Rossi
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  14. Diego Centonze
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Correspondence to Diego Centonze.

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Mori, F., Nicoletti, C.G., Rossi, S. et al. Growth Factors and Synaptic Plasticity in Relapsing–Remitting Multiple Sclerosis. Neuromol Med 16, 490–498 (2014). https://doi.org/10.1007/s12017-014-8297-7

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  • DOI: https://doi.org/10.1007/s12017-014-8297-7

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