Schmidtner, Anna K. and Slattery, David A. and Glaesner, Joachim and Hiergeist, Andreas and Gryksa, Katharina and Malik, Victoria A. and Hellmann-Regen, Julian and Heuser, Isabella and Baghai, Thomas C. and Gessner, Andre and Rupprecht, Rainer and Di Benedetto, Barbara and Neumann, Inga D. (2019) Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner. TRANSLATIONAL PSYCHIATRY, 9: 223. ISSN 2158-3188,
Full text not available from this repository. (Request a copy)Abstract
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 nonselected 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 microbiomegut-brain axis as potential target in the treatment of depression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIDEPRESSANT-LIKE ACTIONS; DEPRESSIVE-LIKE BEHAVIOR; ANIMAL-MODELS; SODIUM-BUTYRATE; RAT MODEL; BRAIN; ACTIVATION; STRESS; ESCITALOPRAM; CITALOPRAM; |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Biology, Preclinical Medicine > Institut für Zoologie Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2020 07:07 |
| Last Modified: | 30 Mar 2020 07:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26260 |
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