Age-dependent spatial memory loss can be partially restored by immune activation
Abstract
Aging is often associated with a decline in hippocampus-dependent spatial memory. Here, we show that functional cell-mediated immunity is required for the maintenance of hippocampus-dependent spatial memory. Sudden imposition of immune compromise in young mice caused spatial memory impairment, whereas immune reconstitution reversed memory deficit in immune-deficient mice. Analysis of hippocampal gene expression suggested that immune-dependent spatial memory performance was associated with the expression of insulin-like growth factor ( Igf1 ) and of genes encoding proteins related to presynaptic activity ( Syt10 , Cplx2 ). We further showed that memory loss in aged mice could be attributed to age-related attenuation of the immune response and could be reversed by immune system activation. Homeostatic-driven proliferation of lymphocytes, which expands the existing T cell repertoire, restored spatial memory deficits in aged mice. Thus, our results identify a novel function of the immune system in the maintenance of spatial memory and suggest an original approach for arresting or reversing age-associated memory loss.
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- Authors
- Ron-Harel, N., Segev, Y., Lewitus, G. M., Cardon, M., Ziv, Y., Netanely, D., Jacob-Hirsch, J., Amariglio, N., Rechavi, G., Domany, E., & Schwartz, M.
- Affiliations
- Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
- Weizmann Institute of Science (IL)
- Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv, Israel.
- Tel Aviv University (IL)
- Sheba Medical Center (IL)
- Venue
- Rejuvenation Research
- Publisher
- SAGE Publications
- Published
- 2008-10
- Volume
- 11
- Issue
- 5
- Pages
- 903-913
- ISSN
- 1094-5458 (ISSN-L)
- 1549-1684
- 1557-8577
- OpenAlex
- W2080635877
- Cited by
- 73
- References
- 5
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 1 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 11 · 2013: 8 · 2012: 2
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Rejuvenation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute on Aging
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- age-related memory decline, spatial memory, hippocampus, cell-mediated immunity, immune reconstitution, immune compromise, insulin-like growth factor I, presynaptic proteins, T cell receptor repertoire, neuroimmunology, cognitive aging
- MeSH terms
- Aging, Animals, Base Sequence, Hippocampus, Immunity, Cellular, Insulin-Like Growth Factor I, Male, Memory Disorders, Mice, Inbred C57BL, Nerve Tissue Proteins, Gene Expression, Bone Marrow Transplantation, Mice, SCID, Microglia, DNA Primers, Maze Learning, Synaptotagmins, Mice
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