Astrocytic TNFα regulates the behavioral response to antidepressants
Abstract
Recent studies have suggested that cytokines, and in particular tumor necrosis factor alpha (TNFα), have a role in modulating antidepressant efficacy. To directly test this idea, we compared the response of TNFα(-/-) mice and astrocyte-specific TNFα(-/-) mice to the antidepressants fluoxetine and desipramine. Using standard behavior models for measuring antidepressant efficacy, the forced swim test (FST) and tail suspension test (TST), we determined that TNFα(-/-) mice were essentially normal in basal behavior in the FST and TST. However, TNFα(-/-) mice showed no behavioral response to a standard dose of chronic antidepressant treatment, in sharp contrast to wildtype mice. Similar results were seen with acute antidepressant treatment, but TNFα(-/-) mice did respond to a very high-dose acute antidepressant treatment. We also assessed in vitro and in vivo effects of fluoxetine on TNFα expression. Glia responded to serotonin in vitro and fluoxetine in vivo by upregulating TNFα mRNA. Consistent with this source of TNFα, mice with an astrocyte-specific deletion of TNFα also did not respond to standard chronic antidepressant treatment. These data suggest that astrocytic TNFα is important to the sensitivity of the behavioral response to administration of antidepressants.
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Suppression of microglia and astrocyte reactivity is implicated in the response to antidepressant therapies.
“Consistently, suppression of microglia [80] and astrocyte [81] reactivity is implicated in the response to antidepressant therapies.”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [81]
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- Authors
- Duseja, R., Heir, R., Lewitus, G. M., Altimimi, H. F., & Stellwagen, D.
- Affiliations
- McGill University Health Centre (CA)
- Corresponding author
- Stellwagen, David
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 44
- Pages
- 187-194
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2030862564
- Cited by
- 25
- References
- 63
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 5
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institute of Health Research
- NARSAD Young Investigator
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TNF-α, astrocytes, antidepressant response, fluoxetine, desipramine, forced swim test, tail suspension test, serotonin, antidepressant sensitivity
- MeSH terms
- Animals, Antidepressive Agents, Astrocytes, Behavior, Animal, Desipramine, Fluoxetine, Mice, Inbred C57BL, Motor Activity, Swimming, Tumor Necrosis Factor-alpha, Mice, Knockout, Hindlimb Suspension, Mice
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