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J Neuroimmunol. 2013 Nov 15;264(1-2):8-13. doi: 10.1016/j.jneuroim.2013.08.009. Epub 2013 Aug 31.

Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis.

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1
Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy; UOC Neurologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.

Abstract

Alterations of glutamate-mediated synaptic transmission occur in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Here we investigated whether intracerebroventricular (Icv) administration of cladribine has effects on EAE. Icv infusion of cladribine reduced the clinical deficits of EAE mice and reversed EAE-induced enhancement of excitatory postsynaptic current (sEPSC) frequency, a neurophysiological measure of glutamatergic synaptopathy associated with central inflammation. Cladribine failed to interfere with EAE-induced microglial and astroglial activation, but blocked EAE synaptic alterations by interfering with interleukin-1β effects. Cladribine possesses neuroprotective properties in experimental MS that are independent of its peripheral immunosuppressant action.

KEYWORDS:

Cladribine; EAE; EPSC; IL-1β; Microglia; Striatum

PMID:
24045165
DOI:
10.1016/j.jneuroim.2013.08.009
[Indexed for MEDLINE]
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