Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain
Open accessAbstract
Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain. However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus. The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration. While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored. Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice. Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging. Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice. Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory. Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.
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STAT3, a transcription factor activated by inflammatory cytokines, is at least in part responsible for NSC differentiation being biased towards glial cells (rather than neurons) during ageing.
“STAT3 — a transcription factor activated by inflammatory cytokines — is at least in part responsible for NSC differentiation being biased towards glial cells (rather than neurons) during ageing46,94.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [94]
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Διερεύνηση τεχνικών παραμέτρων για βέλτιστη σχεδίαση συστημάτων τεχνολογίας Wi-Fi
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- Authors
- Wheatley, E. G., Albarran, E., White, C. W., Bieri, G., Sanchez-Diaz, C., Pratt, K., Snethlage, C. E., Ding, J. B., & Villeda, S. A.
- Affiliations
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Corresponding author
- Villeda, Saul A.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 29
- Issue
- 20
- Pages
- 3359-3369.e4
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC7199460
- OpenAlex
- W2977249793
- Cited by
- 107
- References
- 41
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 16 · 2023: 25 · 2022: 17 · 2021: 14 · 2020: 9 · 2013: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- O-GlcNAcylation, O-GlcNAc transferase, brain aging, cognitive aging, hippocampal neurons, spatial learning and memory, conditional knockout mice, viral overexpression, neurodegeneration
- MeSH terms
- Acetylglucosamine, Acylation, Aging, Animals, Cognition, Male, N-Acetylglucosaminyltransferases, Mice, Knockout, Mice
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