Document Detail

Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.
MedLine Citation:
PMID:  23355887     Owner:  NLM     Status:  MEDLINE    
Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.
Robert Nisticò; Dalila Mango; Georgia Mandolesi; Sonia Piccinin; Nicola Berretta; Marco Pignatelli; Marco Feligioni; Alessandra Musella; Antonietta Gentile; Francesco Mori; Giorgio Bernardi; Ferdinando Nicoletti; Nicola B Mercuri; Diego Centonze
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-23
Journal Detail:
Title:  PloS one     Volume:  8     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-06-24     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e54666     Citation Subset:  IM    
IRCSS Fondazione Santa Lucia, Rome, Italy.
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MeSH Terms
CA1 Region, Hippocampal* / metabolism,  pathology,  physiopathology
Cell Line
Encephalomyelitis, Autoimmune, Experimental* / metabolism,  pathology,  physiopathology
GABAergic Neurons / metabolism,  pathology
Interleukin-1beta / metabolism
Long-Term Potentiation*
Multiple Sclerosis* / metabolism,  pathology,  physiopathology
N-Methylaspartate / metabolism
Synapses* / metabolism,  pathology
Synaptic Transmission*
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism
Reg. No./Substance:
0/Interleukin-1beta; 6384-92-5/N-Methylaspartate; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

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

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