Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging.
Previous studies have suggested that calcium/calmodulin-dependent protein kinase IV (CaMKIV) functions as a positive regulator for memory formation and that age-related memory deficits are the result of dysfunctional signaling pathways mediated by cAMP response element-binding protein (CREB), the downstream transcription factor of CaMKIV. Little is known, however, about the effects of increased CaMKIV levels on the ability to form memory in adult and aged stages. We generated a transgenic mouse overexpressing CaMKIV in the forebrain and showed that the upregulation of CaMKIV led to an increase in learning-induced CREB activity, increased learning-related hippocampal potentiation, and enhanced consolidation of contextual fear and social memories. Importantly, we also observed reduced hippocampal CaMKIV expression with aging and a correlation between CaMKIV expression level and memory performance in aged mice. Genetic overexpression of CaMKIV was able to rescue associated memory deficits in aged mice. Our findings suggest that the level of CaMKIV expression correlates positively with the ability to form long-term memory and implicate the decline of CaMKIV signaling mechanisms in age-related memory deficits.
Fukushima
Hotaka
H
Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan.
Maeda
Ryouta
R
Suzuki
Ryousuke
R
Suzuki
Akinobu
A
Nomoto
Masanori
M
Toyoda
Hiroki
H
Wu
Long-Jun
LJ
Xu
Hui
H
Zhao
Ming-Gao
MG
Ueda
Kenji
K
Kitamoto
Aya
A
Mamiya
Nori
N
Yoshida
Taro
T
Homma
Seiichi
S
Masushige
Shoichi
S
Zhuo
Min
M
Kida
Satoshi
S
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4