title: Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging.
abstract: 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.
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan.
authors.forename: Hotaka
authors.initials: H
authors.lastname: Fukushima
authors.forename: Ryouta
authors.initials: R
authors.lastname: Maeda
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Suzuki
authors.forename: Akinobu
authors.initials: A
authors.lastname: Suzuki
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Toyoda
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
authors.forename: Kenji
authors.initials: K
authors.lastname: Ueda
authors.forename: Aya
authors.initials: A
authors.lastname: Kitamoto
authors.forename: Nori
authors.initials: N
authors.lastname: Mamiya
authors.forename: Taro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Seiichi
authors.initials: S
authors.lastname: Homma
authors.forename: Shoichi
authors.initials: S
authors.lastname: Masushige
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
mesh_terms: 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*
chemical_list: D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4