title: Growth factors and synaptic plasticity in relapsing-remitting multiple sclerosis.
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.
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mori
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Nicoletti
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Caterina
authors.initials: C
authors.lastname: Motta
authors.forename: Hajime
authors.initials: H
authors.lastname: Kusayanagi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergami
authors.forename: Valeria
authors.initials: V
authors.lastname: Studer
authors.forename: Fabio
authors.initials: F
authors.lastname: Buttari
authors.forename: Francesca
authors.initials: F
authors.lastname: Barbieri
authors.forename: Sagit
authors.initials: S
authors.lastname: Weiss
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000328:Adult; D003289:Convalescence; D004576:Electromyography; D019054:Evoked Potentials, Motor; D005260:Female; D005346:Fibroblast Growth Factors / Q000134:cerebrospinal fluid; D016179:Granulocyte Colony-Stimulating Factor / Q000134:cerebrospinal fluid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000134:cerebrospinal fluid; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000134:cerebrospinal fluid / Q000502:physiology*; D012720:Severity of Illness Index; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D010982:Platelet-Derived Growth Factor; D016179:Granulocyte Colony-Stimulating Factor; D005346:Fibroblast Growth Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor