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01-03-2014 | Original Paper

Interleukin-1β Promotes Long-Term Potentiation in Patients with Multiple Sclerosis

Authors: Francesco Mori, Robert Nisticò, Georgia Mandolesi, Sonia Piccinin, Dalila Mango, Hajime Kusayanagi, Nicola Berretta, Alessandra Bergami, Antonietta Gentile, Alessandra Musella, Carolina G. Nicoletti, Ferdinando Nicoletti, Fabio Buttari, Nicola B. Mercuri, Gianvito Martino, Roberto Furlan, Diego Centonze

Published in: NeuroMolecular Medicine | Issue 1/2014

Abstract

The immune system shapes synaptic transmission and plasticity in experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis (MS). These synaptic adaptations are believed to drive recovery of function after brain lesions, and also learning and memory deficits and excitotoxic neurodegeneration; whether inflammation influences synaptic plasticity in MS patients is less clear. In a cohort of 59 patients with MS, we found that continuous theta-burst transcranial magnetic stimulation did not induce the expected long-term depression (LTD)-like synaptic phenomenon, but caused persisting enhancement of brain cortical excitability. The amplitude of this long-term potentiation (LTP)-like synaptic phenomenon correlated with the concentration of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the cerebrospinal fluid. In MS and EAE, the brain and spinal cord are typically enriched of CD3⁺ T lymphocyte infiltrates, which are, along with activated microglia and astroglia, a major cause of inflammation. Here, we found a correlation between the presence of infiltrating T lymphocytes in the hippocampus of EAE mice and synaptic plasticity alterations. We observed that T lymphocytes from EAE, but not from control mice, release IL-1β and promote LTP appearance over LTD, thereby mimicking the facilitated LTP induction observed in the cortex of MS patients. EAE-specific T lymphocytes were able to suppress GABAergic transmission in an IL-1β-dependent manner, providing a possible synaptic mechanism able to lower the threshold of LTP induction in MS brains. Moreover, in vivo blockade of IL-1β signaling resulted in inflammation and synaptopathy recovery in EAE hippocampus. These data provide novel insights into the pathophysiology of MS.

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Title: Interleukin-1β Promotes Long-Term Potentiation in Patients with Multiple Sclerosis
Authors: Francesco Mori
Robert Nisticò
Georgia Mandolesi
Sonia Piccinin
Dalila Mango
Hajime Kusayanagi
Nicola Berretta
Alessandra Bergami
Antonietta Gentile
Alessandra Musella
Carolina G. Nicoletti
Ferdinando Nicoletti
Fabio Buttari
Nicola B. Mercuri
Gianvito Martino
Roberto Furlan
Diego Centonze
Publication date: 01-03-2014
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 1/2014
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-013-8249-7

At a glance: The STEP trials

Springer Medicine

Interleukin-1β Promotes Long-Term Potentiation in Patients with Multiple Sclerosis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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