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Reduced calcium/calmodulin‐dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP‐treated mice
Author(s) -
Moriguchi Shigeki,
Yabuki Yasushi,
Fukunaga Kohji
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07608.x
Subject(s) - mptp , autophosphorylation , endocrinology , neuroscience , medicine , long term potentiation , hippocampal formation , ampa receptor , tyrosine hydroxylase , chemistry , dopaminergic , dopamine , psychology , glutamate receptor , protein kinase a , phosphorylation , biochemistry , receptor
J. Neurochem. (2012) 120 , 541–551. Abstract 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.