The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability
Open accessAbstract
In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.
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Other studies suggest that macrophages contribute to microglial activation, exacerbating pathogenic neuroinflammation.
“while others suggest that macrophages contribute to microglial activation, exacerbating pathogenic neuroinflammation.18,19”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [19]
The Introduction (page unavailable) reports that infiltrating peripheral cells can activate glia, and the Discussion (page unavailable) describes macrophage infiltration into the brain. The paper does not specifically show that macrophages activate microglia or thereby exacerbate neuroinflammation; its own findings concern age-related changes in rats. (LLM, conf=0.82)
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References 56 · Cited by 92
Research works printed but not linked: 3
- Cowley, T.R., O'Sullivan, J., Blau, C., Deighan, B.F., Jones, R., Kerskens, C., Richardson, J.C., Virley, D., Upton, N., Lynch, M.A., 2010. Rosiglitazone attenuates the age-related changes in astrocytosis and the deficit in LTP. Neurobiol. Aging. doi: 10.1016/j.neurobiolaging. 2010.02.002. · DOI
- Paxinos, G., Watson, C., 2004. The Rat Brain in Stereotaxic Co-Ordinates. Academic Press, New York.
- Small, S.A., Chawla, M.K., Buonocore, M., Rapp, P.R., Barnes, C.A., 2004. Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proc. Natl. Acad. Sci. U. S. A. 101, 7181-7186.
- Authors
- Blau, C. W., Cowley, T. R., O'Sullivan, J., Grehan, B., Browne, T. C., Kelly, L., Birch, A., Murphy, N., Kelly, A. M., Kerskens, C. M., & Lynch, M. A.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Cowley, Thelma R.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 33
- Issue
- 5
- Pages
- 1005.e23-1005.e35
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2162545976
- Cited by
- 92
- References
- 56
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 10 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, cc-by-nc-sa)
- Funders
- Russian Science Foundation
- GlaxoSmithKline
- Health Research Board
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- aging, long-term potentiation, synaptic plasticity, blood-brain barrier permeability, cerebral perfusion, T2 relaxation time, microglial activation, CD11b, CD68, MHC class II, infiltrating macrophages, CD45, chemokines, CXCL10, MCP-1, hippocampus, neurodegenerative diseases, early diagnosis
- MeSH terms
- Aging, Animals, Blood-Brain Barrier, Capillary Permeability, Cerebral Cortex, Cerebrovascular Circulation, Hippocampus, Magnetic Resonance Imaging, Male, Rats, Wistar, Long-Term Potentiation, Neurodegenerative Diseases, Rats, Perfusion Imaging
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