Aging leads to prolonged duration of inflammation-induced depression-like behavior caused by Bacillus Calmette-Guérin
Open accessAbstract
Geriatric depression is a costly health issue, but little is known about its physiological underpinnings. Systemic inflammation sensitizes the innate immune system of aged animals and humans, but it is unknown if chronic, low-grade infections affect the duration of depressive-like behaviors. In this report, we infected adult (4-6 months) and aged (20-24 months) Balb/c mice with an attenuated strain of Mycobacterium bovis, Bacillus Calmette-Guérin (BCG), to induce a chronic infection. We then measured depression-like behaviors that have construct, face and predictive validity for human inflammation-associated clinical depression. Exposure to BCG caused acute sickness responses in both adult and aged mice. However, sickness behavior was prolonged in aged mice, as assessed by both locomotor and rearing activity. Two measures of depression-like behavior, which were tests involving sucrose preference and tail suspension, both showed that adult mice displayed depression-like behaviors at one day and seven days after exposure to BCG. However, aged mice continued to express both of these depression-like behaviors at three weeks following infection. Infection with BCG caused an increase in tryptophan catabolism, as evidenced by a significant rise in the plasma kynurenine/tryptophan ratio that peaked at 7 days post-infection. In aged mice, greater tryptophan catabolism persisted longer and remained elevated at 21 days post-infection. This finding is consistent with the prolonged duration of depression-like behaviors in aged mice. These are the first data using a chronic infection model to establish that recovery from inflammation-induced depression-like behavior and tryptophan catabolism are prolonged in aged animals.
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Chronic immune challenge, such as Bacillus Calmette-Guerin, triggered prolonged depressive-like behavior that persisted beyond 21 days.
“However, chronic immune challenge, such as, Bacillus Calmette-Guerin triggered prolonged depressive-like behavior that persisted beyond 21 days (Kelley et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Kelley et al, 2013
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- Authors
- Kelley, K. W., O’Connor, J. C., Lawson, M. A., Dantzer, R., Rodriguez-Zas, S. L., & McCusker, R. H.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 32
- Pages
- 63-69
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3686980
- OpenAlex
- W1993306791
- Cited by
- 49
- References
- 39
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 5 · 2016: 12 · 2015: 6 · 2014: 7 · 2013: 4
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG029573)
- National Institute of Mental Health (R21MH096030, R01MH090127, MH083767, R01MH083767)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- aging, geriatric depression, BCG vaccine, Mycobacterium bovis, chronic infection, sickness behavior, depression-like behavior, tryptophan catabolism, kynurenine/tryptophan ratio, immunosenescence, recovery from depression
- MeSH terms
- Aging, Animals, Behavior, Animal, Body Weight, Chronic Disease, Depression, Inflammation, Kynurenine, Lung, Mice, Inbred BALB C, Motor Activity, Mycobacterium bovis, Mycobacterium Infections, Spleen, Tryptophan, Hindlimb Suspension, Mice, Illness Behavior, Anhedonia
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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