Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging

Hotaka Fukushima, Ryouta Maeda, Ryousuke Suzuki, Akinobu Suzuki, Masanori Nomoto, Hiroki Toyoda, LongJun Wu, Hui Xu, Ming Gao Zhao, Kenji Ueda, Aya Kitamoto, Nori Mamiya, Taro Yoshida, Seiichi Homma, Shoichi Masushige, Min Zhuo, Satoshi Kida

Research output: Contribution to journalArticle

79 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9910-9919
Number of pages10
JournalJournal of Neuroscience
Volume28
Issue number40
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 4
Memory Disorders
Up-Regulation
Cyclic AMP Response Element-Binding Protein
Aptitude
Learning
Long-Term Memory
Prosencephalon
Transgenic Mice
Fear

Keywords

  • Aging
  • CaMKIV
  • CREB
  • Hippocampus
  • Memory consolidation
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging. / Fukushima, Hotaka; Maeda, Ryouta; Suzuki, Ryousuke; Suzuki, Akinobu; Nomoto, Masanori; Toyoda, Hiroki; Wu, LongJun; Xu, Hui; Zhao, Ming Gao; Ueda, Kenji; Kitamoto, Aya; Mamiya, Nori; Yoshida, Taro; Homma, Seiichi; Masushige, Shoichi; Zhuo, Min; Kida, Satoshi.

In: Journal of Neuroscience, Vol. 28, No. 40, 01.10.2008, p. 9910-9919.

Research output: Contribution to journalArticle

Fukushima, H, Maeda, R, Suzuki, R, Suzuki, A, Nomoto, M, Toyoda, H, Wu, L, Xu, H, Zhao, MG, Ueda, K, Kitamoto, A, Mamiya, N, Yoshida, T, Homma, S, Masushige, S, Zhuo, M & Kida, S 2008, 'Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging', Journal of Neuroscience, vol. 28, no. 40, pp. 9910-9919. https://doi.org/10.1523/JNEUROSCI.2625-08.2008
Fukushima, Hotaka ; Maeda, Ryouta ; Suzuki, Ryousuke ; Suzuki, Akinobu ; Nomoto, Masanori ; Toyoda, Hiroki ; Wu, LongJun ; Xu, Hui ; Zhao, Ming Gao ; Ueda, Kenji ; Kitamoto, Aya ; Mamiya, Nori ; Yoshida, Taro ; Homma, Seiichi ; Masushige, Shoichi ; Zhuo, Min ; Kida, Satoshi. / Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 40. pp. 9910-9919.
@article{bf8d0737da8b4d529f91341892f397db,
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.",
keywords = "Aging, CaMKIV, CREB, Hippocampus, Memory consolidation, Transgenic mice",
author = "Hotaka Fukushima and Ryouta Maeda and Ryousuke Suzuki and Akinobu Suzuki and Masanori Nomoto and Hiroki Toyoda and LongJun Wu and Hui Xu and Zhao, {Ming Gao} and Kenji Ueda and Aya Kitamoto and Nori Mamiya and Taro Yoshida and Seiichi Homma and Shoichi Masushige and Min Zhuo and Satoshi Kida",
year = "2008",
month = "10",
day = "1",
doi = "10.1523/JNEUROSCI.2625-08.2008",
language = "English (US)",
volume = "28",
pages = "9910--9919",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "40",

}

TY - JOUR

T1 - Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging

AU - Fukushima, Hotaka

AU - Maeda, Ryouta

AU - Suzuki, Ryousuke

AU - Suzuki, Akinobu

AU - Nomoto, Masanori

AU - Toyoda, Hiroki

AU - Wu, LongJun

AU - Xu, Hui

AU - Zhao, Ming Gao

AU - Ueda, Kenji

AU - Kitamoto, Aya

AU - Mamiya, Nori

AU - Yoshida, Taro

AU - Homma, Seiichi

AU - Masushige, Shoichi

AU - Zhuo, Min

AU - Kida, Satoshi

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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.

AB - 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.

KW - Aging

KW - CaMKIV

KW - CREB

KW - Hippocampus

KW - Memory consolidation

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=54049107769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54049107769&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2625-08.2008

DO - 10.1523/JNEUROSCI.2625-08.2008

M3 - Article

VL - 28

SP - 9910

EP - 9919

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 40

ER -