Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner
Open accessAbstract
Major depressive disorder is the main cause of disability worldwide with imperfect treatment options. However, novel therapeutic approaches are currently discussed, from augmentation strategies to novel treatments targeting the immune system or the microbiome-gut-brain axis. Therefore, we examined the potential beneficial effects of minocycline, a tetracycline antibiotic with pleiotropic, immunomodulatory action, alone or as augmentation of escitalopram on behavior, prefrontal microglial density, and the gut microbiome in rats selectively bred for high anxiety-like behavior (HAB). We show that concomitant with their high innate anxiety and depression, HABs have lower microglial numbers in the infralimbic and prelimbic prefrontal cortex and an altered gut microbiota composition compared with controls. Three weeks of minocycline treatment alleviated the depressive-like phenotype, further reduced microglial density, exclusively in male HAB rats, and reduced plasma concentrations of pro-inflammatory cytokines. However, coadministration of escitalopram, which had no effect alone, prevented these minocycline-induced effects. Moreover, minocycline led to a robust shift in cecal microbial composition in both HABs and rats non-selected for anxiety-like behavior. Minocycline markedly increased relative abundance of Lachnospiraceae and Clostridiales Family XIII, families known for their butyrate production, with a corresponding increase and positive correlation in plasma 3-OH-butyrate levels in a trait-dependent manner. Thus, our data suggest that the antidepressant effect of minocycline is sex- and trait-dependent, associated with a reduced microglial number in the prefrontal cortex, and with changes in microbial composition and their metabolites. These results further support the microbiome-gut–brain axis as potential target in the treatment of depression.
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In animals, minocycline reduces microglial activation in prefrontal cortex and depression- and anxiety-like behaviors.
“minocycline decreases microglial activation in the PFC and depressive and anxiety-like traits in animals (293)”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [293]
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- Authors
- Schmidtner, A. K., Slattery, D. A., Gläsner, J., Hiergeist, A., Gryksa, K., Malik, V. A., Hellmann-Regen, J., Heuser, I., Baghai, T. C., Gessner, A., Rupprecht, R., Di Benedetto, B., & Neumann, I. D.
- Affiliations
- University of Regensburg (DE)
- Goethe University Frankfurt (DE)
- University Hospital Regensburg (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Schmidtner, Anna K.
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2019-09-13
- Volume
- 9
- Issue
- 1
- Pages
- 223-223
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6744405
- OpenAlex
- W2972689719
- Cited by
- 153
- References
- 84
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 22 · 2023: 23 · 2022: 25 · 2021: 34 · 2020: 20
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg)
- Funders
- Bundesministerium für Bildung und Forschung (01EE1401F, 01EE1401B)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- minocycline, major depressive disorder, trait anxiety, gut microbiota, microbiome-gut-brain axis, microglia, prefrontal cortex, escitalopram, antidepressant augmentation, sex differences, butyrate, Lachnospiraceae, inflammatory cytokines, anxiety-like behavior, rats
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Bacterial Agents, Anxiety, Behavior, Animal, Cecum, Disease Models, Animal, Female, Male, Minocycline, Treatment Outcome, Rats, Wistar, Prefrontal Cortex, Microglia, Rats
About these checks
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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