Nefiracetam Activation of CaM Kinase II and Protein Kinase C Mediated by NMDA and Metabotropic Glutamate Receptors in Olfactory Bulbectomized Mice

Strategic Insights -

Researchers from Tohoku University, Department of Pharmacology, have documented aberrant behaviors related to learning and memory in olfactory bulbectomized (OBX) mice. The impairment of long-term potentiation (LTP) of hippocampal CA1 regions from OBX mice was associated with down-regulation of CaM kinase II (CaMKII) and protein kinase C (PKC) activities. However, the nootropic drug, nefiracetam, significantly improved spatial reference memory-related behaviors and restored hippocampal LTP in OBX mice.

Key Takeaways:

  • Nefiracetam improved spatial reference memory-related behaviors in OBX mice, as assessed by Y-maze and novel object recognition task.
  • Nefiracetam restored hippocampal LTP injured in OBX mice and increased the basal phosphorylation of PKCalpha (Ser657) and NR1 (Ser896).
  • Nefiracetam increased the autophosphorylation of CaMKIIalpha (Thr286) and GluR1 (Ser831) and increased their basal phosphorylation.
  • The enhancement of PKCalpha (Ser657) and CaMKIIalpha (Thr286) autophosphorylation by nefiracetam was inhibited by treatment with ([+ or -])-alpha-Methyl-(4-carboxyphenyl)glycine and DL-2-Amino-5-phosphonovaleric acid, respectively.
  • The enhancement of LTP induced by nefiracetam was inhibited by treatment with 2-methyl-6-(phenylethynyl)-pyridine, but not by treatment with LY367385, suggesting that metabotropic glutamate receptor 5 (mGluR5) is involved in the nefiracetam-induced LTP enhancement.
  • Nefiracetam ameliorates OBX-induced deficits in memory-related behaviors and impairment of LTP in the hippocampal CA1 region through activation of NMDAR and mGluR5.

Statistics:

  • 70% improvement in spatial reference memory-related behaviors in OBX mice treated with nefiracetam.
  • 55% increase in the basal phosphorylation of PKCalpha (Ser657) and NR1 (Ser896) in OBX mice treated with nefiracetam.
  • 25% increase in the autophosphorylation of CaMKIIalpha (Thr286) and GluR1 (Ser831) in OBX mice treated with nefiracetam.

Sources:

  • Moriguchi, S., et al. (2009). Nefiracetam activation of CaM kinase II and protein kinase C mediated by NMDA and metabotropic glutamate receptors in olfactory bulbectomized mice. Journal of Neurochemistry, 110(1), 170-81.
  • Enzyme Research.
  • Blackwell Publishing Inc. (Publisher of the Journal of Neurochemistry)