The central nervous system (CNS) and the immune system are known to be engaged in an intense bidirectional crosstalk. In particular, the immune system has the potential to influence the induction of brain plastic phenomena and neuronal networks functioning. During direct CNS inflammation, as well as during systemic, peripheral, inflammation, the modulation exerted by neuroinflammatory mediators on synaptic plasticity might negatively influence brain neuronal networks functioning. The aim of the present study was to investigate, by using electrophysiological techniques, the ability of hippocampal excitatory synapses to undergo synaptic plasticity during the initial clinical phase of an experimental model of CNS (experimental autoimmune encephalomyelitis, EAE) as well as following a systemic inflammatory trigger. Moreover, we compared the morphologic, synaptic and molecular consequences of central neuroinflammation with those accompanying peripheral inflammation. Hippocampal long-term potentiation (LTP) has been studied by extracellular field potential recordings in the CA1 region. Immunohistochemistry was performed to investigate microglia activation. Western blot and ELISA assays have been performed to assess changes in the subunit composition of the synaptic glutamate NMDA receptor and the concentration of pro-inflammatory cytokines in the hippocampus. Significant microglial activation together with an impairment of CA1 LTP was present in the hippocampus of mice with central as well as peripheral inflammation. Interestingly, exclusively during EAE but not during systemic inflammation, the impairment of hippocampal LTP was paralleled by a selective reduction of the NMDA receptor NR2B subunit levels and a selective increase of interleukin-1β (IL1β) levels. Both central and peripheral inflammation-triggered mechanisms can activate CNS microglia and influence the function of CNS synapses. During direct CNS inflammation these events are accompanied by detectable changes in synaptic glutamate receptors subunit composition and in the levels of the pro-inflammatory cytokine IL1β.
|Titolo:||Effects of central and peripheral inflammation on hippocampal synaptic plasticity|
DILUCA, MONICA MARIA GRAZIA (Penultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.1016/j.nbd.2012.12.009|
|Appare nelle tipologie:||01 - Articolo su periodico|