Mori F, Rossi S, Piccinin S, Motta C, Mango D, Kusayanagi H, Bergami A, Studer V, Nicoletti CG, Buttari F, Barbieri F, Mercuri NB, Martino G, Furlan R, Nisticò R, Centonze D. Synaptic Plasticity and PDGF Signaling Defects Underlie Clinical Progression in Multiple Sclerosis.J Neurosci. 2013 Dec 4;33(49):19112-9. doi: 10.1523/JNEUROSCI.2536-13.2013.
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 platelet-derived 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.
As we have said a few times plasticity is how the CNS learns and adapts to change and how if makes new contacts in the nervous circuitry. This study suggests that there may be some problems associated with this particularly in progressive MSers. Long term potentiation (LTP) is part of the process by which memories are formed. In this study there is the suggestion in that in PPMS there are differences in the LTP potential compared to RRMSers. And that this correlates with the amount of platelet derived growth factor is a factor that can come from platelets and other cells and is notable for the stimulation of growth of oligodendrocytes. Is this the effect that is important? However as it has many potential effects delivery into the CNS many be most useful in order to limit unwanted side effects.