Reduced calcium/calmodulin-dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP-treated mice
Article first published online: 6 JAN 2012
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 120, Issue 4, pages 541–551, February 2012
How to Cite
Moriguchi, S., Yabuki, Y. and Fukunaga, K. (2012), Reduced calcium/calmodulin-dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP-treated mice. Journal of Neurochemistry, 120: 541–551. doi: 10.1111/j.1471-4159.2011.07608.x
- Issue published online: 13 JAN 2012
- Article first published online: 6 JAN 2012
- Accepted manuscript online: 2 DEC 2011 09:08AM EST
- Received July 5, 2011; revised manuscript received November 18, 2011; accepted November 29, 2011.
- calcium/calmodulin-dependent protein kinase II;
- cognitive deficits;
- long-term potentiation;
- Parkinson’s disease
J. Neurochem. (2012) 120, 541–551.
Parkinson’s disease (PD) patients frequently reveal deficit in cognitive functions during the early stage in PD. The dopaminergic neurotoxin, MPTP-induced neurodegeneration causes an injury of the basal ganglia and is associated with PD-like behaviors. In this study, we demonstrated that deficits in cognitive functions in MPTP-treated mice were associated with reduced calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and impaired long-term potentiation (LTP) induction in the hippocampal CA1 region. Mice were injected once a day for 5 days with MPTP (25 mg/kg i.p.). The impaired motor coordination was observed 1 or 2 week after MPTP treatment as assessed by rota-rod and beam-walking tasks. In immunoblotting analyses, the levels of tyrosine hydroxylase protein and CaMKII autophosphorylation in the striatum were significantly decreased 1 week after MPTP treatment. By contrast, deficits of cognitive functions were observed 3–4 weeks after MPTP treatment as assessed by novel object recognition and passive avoidance tasks but not Y-maze task. Impaired LTP in the hippocampal CA1 region was also observed in MPTP-treated mice. Concomitant with impaired LTP induction, CaMKII autophosphorylation was significantly decreased 3 weeks after MPTP treatment in the hippocampal CA1 region. Finally, the reduced CaMKII autophosphorylation was closely associated with reduced AMPA-type glutamate receptor subunit 1 (GluR1; Ser-831) phosphorylation in the hippocampal CA1 region of MPTP-treated mice. Taken together, decreased CaMKII activity with concomitant impaired LTP induction in the hippocampus likely account for the learning disability observed in MPTP-treated mice.