Antidepressant effects of Enterococcus faecalis 2001 through the regulation of prefrontal cortical myelination via the enhancement of CREB/BDNF and NF-κB p65/LIF/STAT3 pathways in olfactory bulbectomized mice
| Autor: | Kohei Takahashi, Kazuhiro Kurokawa, Lihua Hong, Kazuya Miyagawa, Atsumi Mochida-Saito, Masahiro Iwasa, Hiroyuki Iwasa, Osamu Nakagawasai, Takeshi Tadano, Hiroshi Takeda, Minoru Tsuji |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
STAT3 Transcription Factor
Depressive Disorder Major Depression Brain-Derived Neurotrophic Factor NF-kappa B Prefrontal Cortex Hippocampus Leukemia Inhibitory Factor Olfactory Bulb Antidepressive Agents Disease Models Animal Mice Psychiatry and Mental health Enterococcus faecalis Animals Humans Cyclic AMP Response Element-Binding Protein Biological Psychiatry |
| Zdroj: | Journal of Psychiatric Research. 148:137-148 |
| ISSN: | 0022-3956 |
| Popis: | A therapeutic strategy through the gut-brain axis has been proven to be effective in treatment for depression. In our previous study, we demonstrated that Enterococcus faecalis 2001 (EF-2001) prevents colitis-induced depressive-like behavior through the gut-brain axis in mice. More recently, we found that demyelination in the prefrontal cortex (PFC) was associated with depressive-like behavior in an animal model of major depressive disorder, olfactory bulbectomized (OBX) mice. The present study investigated the effects of EF-2001 on depressive-like behaviors in OBX mice and the underlying molecular mechanisms from the perspective of myelination in the PFC. OBX mice exhibited depressive-like behaviors in the tail-suspension, splash, and sucrose preference tests, and decreased myelin and paranodal proteins along with mature oligodendrocytes in the PFC. These behavioral and biochemical changes were all prevented by treatment with EF-2001. Further, EF-2001 treatment increased brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) in the PFC. Interestingly, an immunohistochemical analysis revealed enhanced phospho (p) -cAMP-responsive element binding protein (CREB) expression in neurons, p-nuclear factor-kappa B (NFκB) p65 (Ser536) expression in astrocytes, and p-signal transducer and activator of transcription 3 (STAT3) (Ty705) expression in mature oligodendrocytes in the PFC of OBX mice. From these results, we suggest that EF-2001 administration prevents depressive-like behaviors by regulating prefrontal cortical myelination via the enhancement of CREB/BDNF and NFκB p65/LIF/STAT3 pathways. Our findings strongly support the idea that a therapeutic strategy involving the gut microbiota may be a promising alternative treatment for alleviating symptoms of depression. |
| Databáze: | OpenAIRE |
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