Document Detail


Laquinimod prevents inflammation-induced synaptic alterations occurring in experimental autoimmune encephalomyelitis.
MedLine Citation:
PMID:  23232603     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND There are two generally accepted strategies for treating multiple sclerosis (MS), preventing central nervous system (CNS) damage indirectly through immunomodulatory interventions and/or repairing CNS damage by promoting remyelination. Both approaches also provide neuroprotection since they can prevent, indirectly or directly, axonal damage. OBJECTIVE Recent experimental and clinical evidence indicates that the novel immunomodulatory drug laquinimod can exert a neuroprotective role in MS. Whether laquinimod-mediated neuroprotection is exerted directly on neuronal cells or indirectly via peripheral immunomodulation is still unclear. METHODS C57Bl/6 experimental autoimmune encephalomyelitis (EAE) mice, immunised with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide, were treated for 26 days with subcutaneous daily injections of laquinimod (from 1 to 25 mg/kg). Patch clamp electrophysiology was performed on acute brain striatal slices from EAE mice treated with daily (25 mg/kg) laquinimod and on acute brain striatal slices from control mice bathed with laquinimod (1-30 µM). RESULTS Both preventive and therapeutic laquinimod treatment fully prevented the alterations of GABAergic synapses induced by EAE, the first limiting also glutamatergic synaptic alterations. This dual effect might, in turn, have limited glutamatergic excitotoxicity, a phenomenon previously observed early during EAE and possibly correlated with later axonal damage. Furthermore, laquinimod treatment also preserved cannabinoid CB1 receptor sensitivity, normally lost during EAE. Finally, laquinimod per se was able to regulate synaptic transmission by increasing inhibitory post-synaptic currents and, at the same time, reducing excitatory post-synaptic currents. CONCLUSIONS Our data suggest a novel neuroprotective mechanism by which laquinimod might in vivo protect from neuronal damage occurring as a consequence of inflammatory immune-mediated demyelination.
Authors:
Francesca Ruffini; Silvia Rossi; Andrea Bergamaschi; Elena Brambilla; Annamaria Finardi; Caterina Motta; Valeria Studer; Francesca Barbieri; Valentina De Chiara; Liat Hayardeny; Giancarlo Comi; Diego Centonze; Gianvito Martino
Related Documents :
23543873 - Microglial control of neuronal activity.
23688543 - Responses of single neurons and neuronal ensembles in frog first- and second-order olfa...
19531533 - Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by m...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-12
Journal Detail:
Title:  Multiple sclerosis (Houndmills, Basingstoke, England)     Volume:  -     ISSN:  1477-0970     ISO Abbreviation:  Mult. Scler.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9509185     Medline TA:  Mult Scler     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Hospital, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The effect of plasma exchange on serum anti-JC virus antibodies.
Next Document:  Wired on sugar: the role of the CNS in the regulation of glucose homeostasis.