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. (April 2022)

• Record Type: Journal Article
• Authors: Takahashi, Kohei; Kurokawa, Kazuhiro; Hong, Lihua; Miyagawa, Kazuya; Mochida-Saito, Atsumi; Iwasa, Masahiro; Iwasa, Hiroyuki; Nakagawasai, Osamu; Tadano, Takeshi; Takeda, Hiroshi; Tsuji, Minoru
• Is Part Of: Journal of psychiatric research. Volume 148(2022)
• Page Start: 137
• Page End: 148
• Publication Date: 2022-04
• Subjects: Depression -- EF-2001 -- Myelin -- Olfactory bulbectomy -- Oligodendrocyte -- Prefrontal cortex; Psychiatry -- Periodicals; Mental Disorders -- Periodicals; Maladies mentales -- Périodiques; Psychiatry; Electronic journals; Periodicals; 616.89005
• DOI: 10.1016/j.jpsychires.2022.01.047
• Languages: English
• ISSNs: 0022-3956

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: OBX mice exhibited depressive-like behaviors. Myelin and paranodal proteins, along with mature oligodendrocytes, were reduced in the PFC of OBX mice. EF-2001 prevented OBX-induced depressive-like behaviors and disturbance of myelination. EF-2001 enhanced the CREB/BDNF and NFκB p65/LIF/STAT3 pathways in the PFC of OBX mice.