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Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis
Alessandra Musella1, Georgia Mandolesi, Antonietta Gentile
1Fondazione 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.
Journal of Neuroimmunology
|September 19, 2013
Summary
Cladribine, delivered intracerebroventricularly, reduced multiple sclerosis (MS) symptoms in mice by protecting against synaptic damage. This neuroprotection occurred independently of its immunosuppressive effects.
Area of Science:
- Neuroimmunology
- Neuropharmacology
- Neurophysiology
Background:
- Multiple sclerosis (MS) involves glutamate-mediated synaptic transmission alterations.
- Experimental autoimmune encephalomyelitis (EAE) models MS, exhibiting similar synaptic dysfunction.
- Central nervous system inflammation in EAE impacts glutamatergic synapses.
Purpose of the Study:
- To investigate the effects of intracerebroventricular (Icv) cladribine administration on EAE.
- To determine if cladribine offers neuroprotection in experimental MS.
- To elucidate the mechanism of cladribine's action on synaptic alterations in EAE.
Main Methods:
- Intracerebroventricular (Icv) infusion of cladribine in EAE mice.
- Assessment of clinical EAE scores.
- Electrophysiological recordings to measure excitatory postsynaptic current (sEPSC) frequency.
- Evaluation of microglial and astroglial activation.
- Analysis of interleukin-1β (IL-1β) involvement.
Main Results:
- Icv cladribine administration significantly reduced clinical deficits in EAE mice.
- Cladribine reversed the EAE-induced enhancement of sEPSC frequency, indicating protection against glutamatergic synaptopathy.
- Cladribine did not affect EAE-induced microglial or astroglial activation.
- Cladribine blocked EAE synaptic alterations by interfering with interleukin-1β effects.
Conclusions:
- Intracerebroventricular cladribine exhibits neuroprotective properties in experimental MS (EAE).
- Cladribine's neuroprotection in EAE is mediated by interfering with IL-1β effects on synaptic function.
- These neuroprotective effects are independent of cladribine's peripheral immunosuppressant actions.
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