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Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering
Open accessAbstract
Significance: Aging is often accompanied by cognitive decline. It is of critical importance to understand the synaptic susceptibilities of the glutamatergic neural circuits to age-related cognitive decline and to intervene in this process. Maintenance of synaptic health in the face of aging is a crucially important therapeutic goal. We show that the glutamate modulator, riluzole, prevents age-related memory loss and induces clustering of dendritic spines. Clustering is a critical element of synaptic plasticity that has been previously demonstrated to increase synaptic strength. This study further elucidates neuroplastic changes in the neurocircuits vulnerable to aging and advances therapeutic development to prevent and treat age-related cognitive decline.
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“During aging in the rat, treatment with riluzole, which is known to retard glutamate release and promote glutamate reuptake by astrocytes, retards aging in the hippocampus as measured by preservation of spatial memory and thin spines that are found in young hippocampal neurons.”
From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [54]
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Metadata
- Authors
- Pereira, A. C., Lambert, H. K., Grossman, Y. S., Dumitriu, D., Waldman, R., Jannetty, S. K., Calakos, K., Janssen, W. G., McEwen, B. S., & Morrison, J. H.
- Affiliations
- Rockefeller University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories,
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-12-15
- Volume
- 111
- Issue
- 52
- Pages
- 18733-18738
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4284552
- OpenAlex
- W2072639715
- Cited by
- 116
- References
- 51
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 13 · 2021: 12 · 2020: 13 · 2019: 13 · 2018: 6 · 2017: 13 · 2016: 15 · 2015: 8
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Dana Foundation (no number)
- Stavros Niarchos Foundation (SNF) (no number)
- HHS | NIH | National Center for Advancing Translational Sciences (NCATS) (8 UL1 TR000043)
- HHS | NIH | National Institute on Aging (U.S. National Institute on Aging) (R37 AG06647)
- Alzheimer Drug Discovery Foundation (ADDF) (20120703)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- age-related cognitive decline, riluzole, glutamatergic synapses, hippocampal CA1, synaptic plasticity, glutamate uptake, extrasynaptic NMDA receptors, memory, synaptic loss, neuroprotection
- MeSH terms
- Aging, Animals, Cognition, Dendrites, Male, Memory, Synaptic Transmission, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Prefrontal Cortex, Neuroprotective Agents, Glutamic Acid, Riluzole, Rats, CA1 Region, Hippocampal
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