Decreased calcium/calmodulin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice

Shigeki Moriguchi, Feng Han, Osamu Nakagawasai, Takeshi Tadano, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

Olfactory bulbectomized (OBX) mice showed significant impairment of learning and memory-related behaviors 14 days after olfactory bulbectomy, as measured by passive avoidance and Y-maze tasks. We here observed a large impairment of hippocampal long-term potentiation (LTP) in the OBX mice. Concomitant with decreased acetylcholinesterase expression, protein kinase C (PKC)α autophosphorylation and NR1(Ser-896) phosphorylation significantly decreased in the hippocampal CA1 region of OBX mice. Both PKCα and NR1(Ser-896) phosphorylation significantly increased following LTP in the control mice, whereas increases were not observed in OBX mice. Like PKC activities, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation significantly decreased in the hippocampal CA1 region of OBX mice as compared with that of control mice. In addition, increased CaMKII autophosphorylation following LTP was not observed in OBX mice. Finally, the impairment of CaMKII autophosphorylation was closely associated with reduced pGluR1(Ser-831) phosphorylation, without change in synapsin I (site 3) phosphorylation in the hippocampal CA1 region of OBX mice. Taken together, in OBX mice NMDA receptor hypofunction, possibly through decreased PKCα activity, underlies decreased CaMKII activity in the post-synaptic regions, thereby impairing LTP induction in the hippocampal CA1 region. Both decreased PKC and CaMKII activities with concomitant LTP impairment account for the learning disability observed in OBX mice.

Original languageEnglish
Pages (from-to)22-29
Number of pages8
JournalJournal of Neurochemistry
Volume97
Issue number1
DOIs
Publication statusPublished - 2006 Apr

Keywords

  • Calcium
  • Calmodulin-dependent protein kinase II
  • Long-term potentiation
  • NMDA
  • Olfactory bulbectomy
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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