Improvement of memory for context by inhibition of caspase‐1 in aged rats
Abstract
Impaired learning and memory is a common pathologic feature associated with numerous neurologic disorders. There is strong evidence that central inflammation contributes significantly to the progression of several neurodegenerative diseases as well as to the ageing process. For example, in aged rats an increase in interleukin‐1β (IL‐1β) is implicated in the decline of synaptic plasticity in the hippocampus and impaired performance on cognitive tasks such as contextual fear conditioning. IL‐1β is a proinflammatory cytokine initially synthesized in an inactive precursor form that is cleaved by caspase‐1 to generate the biologically mature form. In the present study, cleavage of IL‐1β was chronically inhibited using a specific caspase‐1 inhibitor (Ac‐YVAD‐CMK; 10 pmol) in both aged (22 month) and young (4 month) rats. Both groups received Ac‐YVAD‐CMK for 28 days intracerebroventricularly through a brain infusion cannula connected to an osmotic minipump. On day 20 the animals were trained in contextual fear conditioning, and memory for context was tested on day 22. Chronic infusion of a specific caspase‐1 inhibitor in aged rats ameliorated age‐related increases in hippocampal IL‐1β and improved memory for context.
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Elevated IL-1β was reported in some studies and not others; aged Wistar and Fisher 344 rats were reported to show elevated brain IL-1β, whereas other strains did not exhibit increased baseline levels of brain IL-1β.
“For instance, aged (~22 month old) Wistar and Fisher 344 rats (Gemma et al, 2005;Lynch, 1999) were reported to show elevated brain IL-1β, whereas (23-26 month old) Fisher 344 × BN F1 and Fisher 344 rats (Barrientos et al, 2009;Gee, Ding, and Keller, 2006) and (18-22 month old) BALB/c and C57BL/6 mice did not exhibit increased baseline levels of brain IL-1β (Hascup et al, 2016;Huang et al, 2008;Wyn”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Gemma et al, 2005
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- Authors
- Gemma, C., Fister, M., Hudson, C., & Bickford, P. C.
- Affiliations
- University of South Florida (US)
- James A. Haley Veterans' Hospital (US)
- Corresponding author
- Bickford, Paula C.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2005-10
- Volume
- 22
- Issue
- 7
- Pages
- 1751-1756
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2131677266
- Cited by
- 74
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- caspase-1 inhibition, IL-1β, age-related memory impairment, contextual fear conditioning, hippocampus, neuroinflammation, aging, Ac-YVAD-cmk, intracerebroventricular infusion, synaptic plasticity
- MeSH terms
- Age Factors, Aging, Amino Acid Chloromethyl Ketones, Analysis of Variance, Animals, Conditioning, Psychological, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Fear, Interleukin-1, Male, Memory, Rats, Inbred F344, Cysteine Proteinase Inhibitors, Cytokines, Caspases, Caspase 1, Rats, Caspase 3, Caspase Inhibitors
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