TY - JOUR
T1 - Dysfunction of na + /ca 2+ exchangers is associated with cognitive decline in alzheimer’s disease
AU - Moriguchi, Shigeki
AU - Kita, Satomi
AU - Iwamoto, Takahiro
AU - Fukunaga, Koji
N1 - Publisher Copyright:
© 2018, Japanese Pharmacological Society. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Na + /Ca 2+ exchanger (NCX) is mainly expressed in the plasma membrane and mediates electrogenical exchange of one Ca 2+ for three Na + , depending on the electrochemical gradients across the plasma membrane. NCX has three different isoforms (NCX1, NCX2, NCX3) encoded by distinct genes in mammals. Here, we report that NCX2 and NCX3 protein levels are relatively reduced in hippocampal CA1 of Alzheimer’s disease model mice. Likewise, NCX2 +/− or NCX3 +/− mice exhibited impaired hippocampal LTP and memory-related behaviors. In immunoblot analyses, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation significantly decreased in hippocampal CA1 of NCX2 +/− mice compared to wild-type mice. By contrast, NCX2 +/− mice was correlated with elevated calcineurin (CaN) activity and rescued by treatment with the calcineurin inhibitor FK506. Taken together, the imbalance of CaMKII and CaN activities with concomitant LTP impairment likely accounts for the learning disability observed in NCX2 +/− mice.
AB - Na + /Ca 2+ exchanger (NCX) is mainly expressed in the plasma membrane and mediates electrogenical exchange of one Ca 2+ for three Na + , depending on the electrochemical gradients across the plasma membrane. NCX has three different isoforms (NCX1, NCX2, NCX3) encoded by distinct genes in mammals. Here, we report that NCX2 and NCX3 protein levels are relatively reduced in hippocampal CA1 of Alzheimer’s disease model mice. Likewise, NCX2 +/− or NCX3 +/− mice exhibited impaired hippocampal LTP and memory-related behaviors. In immunoblot analyses, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation significantly decreased in hippocampal CA1 of NCX2 +/− mice compared to wild-type mice. By contrast, NCX2 +/− mice was correlated with elevated calcineurin (CaN) activity and rescued by treatment with the calcineurin inhibitor FK506. Taken together, the imbalance of CaMKII and CaN activities with concomitant LTP impairment likely accounts for the learning disability observed in NCX2 +/− mice.
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U2 - 10.1254/fpj.152.299
DO - 10.1254/fpj.152.299
M3 - Article
C2 - 30531101
AN - SCOPUS:85058591246
VL - 152
SP - 299
EP - 305
JO - Folia Pharmacologica Japonica
JF - Folia Pharmacologica Japonica
SN - 0015-5691
IS - 6
ER -