Platelet-activating factor-induced synaptic facilitation is associated with increased calcium/calmodulin-dependent protein kinase II, protein kinase C and extracellular signal-regulated kinase activities in the rat hippocampal CA1 region

S. Moriguchi, N. Shioda, Y. Yamamoto, K. Fukunaga

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Platelet-activating factor (PAF) is an important inflammatory lipid mediator affecting neural plasticity. In the present study, we demonstrated how PAF affects synaptic efficacy through activation of protein kinases in the rat hippocampal CA1 region. In cultured hippocampal neurons, 10 to 1000 nM PAF stimulated autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of synapsin I and myristoylated alanine-rich protein kinase C substrate (MARCKS). In hippocampal CA1 slices, field excitatory postsynaptic potentials (fEPSPs) induced by stimulation of the Schaffer collateral/commissural pathways were significantly increased 10-50 min after exposure to 100 to 1000 nM PAF. Immunoblotting analysis showed that 100 nM PAF treatment for 10 or 50 min significantly and persistently increased CaMKII autophosphorylation in the hippocampal CA1 region. Increased protein kinase Cα (PKCα) autophosphorylation was also seen at the same time point after PAF exposure. By contrast, extracellular signal-regulated kinase (ERK) phosphorylation was slightly but significantly increased at 10 min after PAF exposure. Consistent with increased CaMKII autophosphorylation, AMPA-type glutamate receptor subunit 1 (GluR1) (Ser-831) phosphorylation as a CaMKII postsynaptic substrate significantly increased after 10 or 50 min of treatment, whereas synapsin I (Ser-603) phosphorylation as a presynaptic substrate increased at 10 min in the hippocampal CA1 region. Phosphorylation of MARCKS (Ser-152/156) and NMDA receptor subunit 1 (NR1) (Ser-896) as PKCα substrates also significantly increased after 10 min but had not further increased by 50 min in the CA1 region. Increased of fEPSPs induced by PAF treatment completely and/or partly inhibited by KN93 and/or U0126 treatment. These results suggest that PAF induces synaptic facilitation through activation of CaMKII, PKC and ERK in the hippocampal CA1 region.

Original languageEnglish
Pages (from-to)1158-1166
Number of pages9
JournalNeuroscience
Volume166
Issue number4
DOIs
Publication statusPublished - 2010 Apr 14

Keywords

  • CaMKII
  • ERK
  • PKC
  • platelet-activating factor
  • synaptic facilitation

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Platelet-activating factor-induced synaptic facilitation is associated with increased calcium/calmodulin-dependent protein kinase II, protein kinase C and extracellular signal-regulated kinase activities in the rat hippocampal CA1 region'. Together they form a unique fingerprint.

Cite this