SIRT1 is essential for normal cognitive function and synaptic plasticity

Shaday Michán, Ying Li, Maggie Meng Hsiu Chou, Edoardo Parrella, Huanying Ge, Jeffrey M. Long, Joanne S. Allard, Kaitlyn Lewis, Marshall Miller, Wei Xu, Ronald F. Mervis, Jing Chen, Karen I. Guerin, Lois E.H. Smith, Michael W. McBurney, David A. Sinclair, Michel Baudry, Rafael De Cabo, Valter D. Longo

Research output: Contribution to journalArticle

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Abstract

Conservation of normal cognitive functions relies on the proper performance of the nervous system at the cellular and molecular level. The mammalian nicotinamide-adenine dinucleotide-dependent deacetylase SIRT1 impacts different processes potentially involved in the maintenance of brain integrity, such as chromatin remodeling, DNA repair, cell survival, and neurogenesis. Here we show that SIRT1 is expressed in neurons of the hippocampus, a key structure in learning and memory. Using a combination of behavioral and electrophysiological paradigms, we analyzed the effects of SIRT1 deficiency and overexpression on mouse learning and memory as well as on synaptic plasticity. We demonstrated that the absence of SIRT1 impaired cognitive abilities, including immediate memory, classical conditioning, and spatial learning. In addition, we found that the cognitive deficits in SIRT1 knock-out (KO) mice were associated with defects in synaptic plasticity without alterations in basal synaptic transmission or NMDA receptor function. Brains of SIRT1-KO mice exhibited normal morphology and dendritic spine structure but displayed a decrease in dendritic branching, branch length, and complexity of neuronal dendritic arbors. Also, a decrease in extracellular signal-regulated kinase 1/2 phosphorylation and altered expression of hippocampal genes involved in synaptic function, lipid metabolism, and myelination were detected in SIRT1-KO mice. In contrast, mice with high levels of SIRT1 expression in brain exhibited regular synaptic plasticity and memory. We conclude that SIRT1 is indispensable for normal learning, memory, and synaptic plasticity in mice.

Original languageEnglish (US)
Pages (from-to)9695-9707
Number of pages13
JournalJournal of Neuroscience
Volume30
Issue number29
DOIs
StatePublished - Jul 21 2010

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Neuronal Plasticity
Cognition
Knockout Mice
Learning
Brain
Dendritic Spines
Neurotransmitter Receptor
Aptitude
Chromatin Assembly and Disassembly
Classical Conditioning
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Neurogenesis
N-Methyl-D-Aspartate Receptors
Short-Term Memory
Lipid Metabolism
Synaptic Transmission
DNA Repair
NAD
Nervous System

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Michán, S., Li, Y., Chou, M. M. H., Parrella, E., Ge, H., Long, J. M., ... Longo, V. D. (2010). SIRT1 is essential for normal cognitive function and synaptic plasticity. Journal of Neuroscience, 30(29), 9695-9707. https://doi.org/10.1523/JNEUROSCI.0027-10.2010

SIRT1 is essential for normal cognitive function and synaptic plasticity. / Michán, Shaday; Li, Ying; Chou, Maggie Meng Hsiu; Parrella, Edoardo; Ge, Huanying; Long, Jeffrey M.; Allard, Joanne S.; Lewis, Kaitlyn; Miller, Marshall; Xu, Wei; Mervis, Ronald F.; Chen, Jing; Guerin, Karen I.; Smith, Lois E.H.; McBurney, Michael W.; Sinclair, David A.; Baudry, Michel; De Cabo, Rafael; Longo, Valter D.

In: Journal of Neuroscience, Vol. 30, No. 29, 21.07.2010, p. 9695-9707.

Research output: Contribution to journalArticle

Michán, S, Li, Y, Chou, MMH, Parrella, E, Ge, H, Long, JM, Allard, JS, Lewis, K, Miller, M, Xu, W, Mervis, RF, Chen, J, Guerin, KI, Smith, LEH, McBurney, MW, Sinclair, DA, Baudry, M, De Cabo, R & Longo, VD 2010, 'SIRT1 is essential for normal cognitive function and synaptic plasticity', Journal of Neuroscience, vol. 30, no. 29, pp. 9695-9707. https://doi.org/10.1523/JNEUROSCI.0027-10.2010
Michán S, Li Y, Chou MMH, Parrella E, Ge H, Long JM et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. Journal of Neuroscience. 2010 Jul 21;30(29):9695-9707. https://doi.org/10.1523/JNEUROSCI.0027-10.2010
Michán, Shaday ; Li, Ying ; Chou, Maggie Meng Hsiu ; Parrella, Edoardo ; Ge, Huanying ; Long, Jeffrey M. ; Allard, Joanne S. ; Lewis, Kaitlyn ; Miller, Marshall ; Xu, Wei ; Mervis, Ronald F. ; Chen, Jing ; Guerin, Karen I. ; Smith, Lois E.H. ; McBurney, Michael W. ; Sinclair, David A. ; Baudry, Michel ; De Cabo, Rafael ; Longo, Valter D. / SIRT1 is essential for normal cognitive function and synaptic plasticity. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 29. pp. 9695-9707.
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AU - Long, Jeffrey M.

AU - Allard, Joanne S.

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AU - Xu, Wei

AU - Mervis, Ronald F.

AU - Chen, Jing

AU - Guerin, Karen I.

AU - Smith, Lois E.H.

AU - McBurney, Michael W.

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