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SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity
Open accessAbstract
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.
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In the citing paper
“class III HDAC (i.e., SIRT), which deacetylates histones and nonhistone proteins, also appears to be associated with hippocampal neuroplasticity and depression-like behavior.151–153”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [153]
Experimental — accuracy not yet measuredIn the citing paper
“Also, SIRT1 knockout mice showed decreased dendritic branching, branch length, and complexity of dendritic arbors.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [88]
In the citing paper
“Moreover, SIRT1 knockout mice exhibited altered hippocampal expression of genes with known functions in synaptic and structural plasticity.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [88]
In the citing paper
“SIRT1 knockout mice or mice expressing catalytically inactive SIRT1 showed defects in cognition and hippocampal synaptic plasticity.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [88]
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Cristòfol, R. M., Porquet, D., Corpas, R., Coto‐Montes, A. M., Serret, J., Camins, A., Pallàs, M., & Sanfeliu, C. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00939.x · Cited by 102
Berberine ameliorates doxorubicin-induced cognitive impairment (chemobrain) in rats
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Obesity Weighs down Memory through a Mechanism Involving the Neuroepigenetic Dysregulation of Sirt1
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Sarubbo, F., Ramis, M. R., Kienzer, C., Aparicio, S., Esteban, S., Miralles, A., & Moranta, D. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9759-0 · Cited by 94
Islam, F., Nafady, M. H., Islam, M. R., Saha, S., Rashid, S., Akter, A., Harun-Or-Rashid, M., Akhtar, M. F., Perveen, A., Ashraf, G. M., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02859-7 · Cited by 95
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Metabolic and Neuropsychiatric Effects of Calorie Restriction and Sirtuins
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Mitochondrial SIRT3 and neurodegenerative brain disorders
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Over-expression of miR-34a induces rapid cognitive impairment and Alzheimer’s disease-like pathology
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Aging and brain rejuvenation as systemic events
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Mitochondrial Metabolism-Mediated Regulation of Adult Neurogenesis
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Epigenetics in Alzheimer’s Disease
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Martins, I. J. (2017) · Diabetes & Metabolic Disorders · doi:10.24966/dmd-201x/100019 · Cited by 84
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Metadata
- Authors
- Michan, S., Li, Y., Chou, M. M.-H., Parrella, E., Ge, H., Long, J. M., Allard, J. S., Lewis, K., Miller, M., Xu, W., Mervis, R. F., Chen, J., Guerin, K. I., Smith, L. E. H., McBurney, M. W., Sinclair, D. A., Baudry, M., de Cabo, R., & Longo, V. D.
- Affiliations
- University of Southern California (US)
- National Institutes of Health (US)
- University of South Florida (US)
- Harvard University (US)
- University of Ottawa (CA)
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-07-21
- Volume
- 30
- Issue
- 29
- Pages
- 9695-9707
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2921958
- OpenAlex
- W2075043109
- Cited by
- 541
- References
- 77
- Citations by year
- 2026: 26 · 2025: 29 · 2024: 31 · 2023: 29 · 2022: 51 · 2021: 63 · 2020: 36 · 2019: 26 · 2018: 41 · 2017: 35 · 2016: 26 · 2015: 28 · 2014: 31 · 2013: 32 · 2012: 24
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- Ellison Medical Foundation
- Glenn Foundation for Medical Research
- University of Southern California
- Fondation pour la Recherche Médicale
- National Institutes of Health
- Manton Center for Orphan Disease Research, Boston Children's Hospital
- Canadian Institutes of Health Research
- National Institute on Aging (K01AG001028, P01AG027916, R01AG028730, R01AG019719)
- National Eye Institute (EY017017, EY017017 04S1, R01EY017017)
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- SIRT1, cognitive function, learning and memory, synaptic plasticity, hippocampus, dendritic spine morphology, dendritic branching, ERK1/2 phosphorylation, lipid metabolism, myelination, NMDA receptor, classical conditioning, spatial learning, immediate memory, SIRT1 knockout mice
- MeSH terms
- Animals, Cognition, Gene Expression Regulation, Hippocampus, Learning, Memory, Neurons, Tissue Distribution, Long-Term Potentiation, Mice, Knockout, Patch-Clamp Techniques, Dendritic Spines, Mice, Sirtuin 1
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