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- Title
Upregulation of Calcium/Calmodulin-Dependent Protein Kinase IV Improves Memory Formation and Rescues Memory Loss with Aging.
- Authors
Fukushima, Hotaka; Maeda, Ryouta; Suzuki, Ryousuke; Suzuki, Akinobu; Nomoto, Masanori; Toyoda, Hiroki; Long-Jun Wu; Hui Xu; Ming-Gao Zhao; Ueda, Kenji; Kitamoto, Aya; Mamiya, Nori; Yoshida, Taro; Homma, Seiichi; Masushige, Shoichi; Min Zhuo; Kida, Satoshi
- 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 increasedCaMKIVlevels on the ability to formmemoryin adult and aged stages.Wegenerated a transgenic mouse overexpressingCaMKIV in the forebrain and showed that the upregulation of CaMKIV led to an increase in learning-induced CREB activity, increased learningrelated 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.
- Subjects
NEUROSCIENCES; NEUROBIOLOGY; MEMORY loss; PROTEIN kinases; TRANSCRIPTION factors; CARRIER proteins
- Publication
Journal of Neuroscience, 2008, Vol 28, Issue 40, p9910
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2625-08.2008