Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression
Abstract
Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary. Herein, iTRAQ coupled with LC-MS/MS was applied to compare the OB proteome between "pathological microbiota" and "healthy microbiota" germ-free mice. A set of 367 proteins were differentially identified in the OB, including 119 up-regulated and 248 down-regulated proteins compared with the levels in controls. A combined analysis with significantly changed OB proteins from CUMS depression model supported the role of CREB signaling, whose dysregulation is likely to disrupt the axonogenesis of OB under microbiota condition. With that, the down-regulated CACNA1E and its downstream proteins (CALM/ CaMKII/ CREB/ BDNF) in CREB pathway were validated by Western blot. Meanwhile, the canonical pathways involved Nuclear Receptor Signaling highlighted the fecal microbiota transplantation (FMT) model, which would be a new breakthrough for depressive research. These findings enrich the previous research achievements about the gut microbiota in psychiatric disorders, providing a creative insight into the intricate mechanisms of OB dysfunction in depression. SIGNIFICANCE: Emerging evidence has shown that gut microbiota can greatly influence brain functions and even behaviors. As one of the post-developmental neurogenesis areas for the adult brain, the OB is becoming increasingly important in the study of the pathogenesis of depression. Using an iTRAQ-based proteomics, we identified 367 altered proteins in the OB of fecal microbiota transplanted mouse, which provide a novel insight for further research of the "microbiota-gut-brain axis". In addition, combined analyses with the CUMS depression model and the validation of key proteins by Western blot may assist in the investigation of OB dysfunction in mental sickness.
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FMT from patients with depression to germ-free mice can result in depression-like behaviour in recipient mice.
“These four studies all support that FMT from patients with depression to GF mice can result in depression-like behaviour in the recipient mice.”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [36]
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Mood Disorders: The Gut Bacteriome and Beyond
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Self-citationThe Microbiota‐Gut‐Brain Connection: A New Horizon in Neurological and Neuropsychiatric Disorders
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Self-citationProteomic and metabolomic characterization of amygdala in chronic social defeat stress rats
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Self-citationMolecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3
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Microbial Regulation of a Lincrna–miRNA–mRNA Network in the Mouse Hippocampus
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Self-citationJust a gut feeling: Faecal microbiota transplant for treatment of depression – A mini-review
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Commensal Microbiota Regulation of Metabolic Networks During Olfactory Dysfunction in Mice
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Genome-wide DNA methylation profiling and gut flora analysis in intestinal polyps patients
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Self-citationOptimization of potential targets for antidepressant Chinese medicines: AI and multi-omics methods
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Upregulation of C1QC as a Mediator of Blood–Brain Barrier Damage in Type 2 Diabetes Mellitus
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Gut microbiota: a new insight into neuropsychiatric disorders
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Self-citationPM2.5 induced neurotoxicity and depression unveiling exposure risks and mechanistic insights
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- Authors
- Huang, C., Yang, X., Zeng, B., Zeng, L., Gong, X., Zhou, C., Xia, J., Lian, B., Qin, Y., Yang, L., Liu, L., & Xie, P.
- Affiliations
- Chongqing Medical University (CN)
- Army Medical University (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- Xie, Peng
- ORCID
- Venue
- Journal of Proteomics
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 194
- Pages
- 132-147
- ISSN
- 1874-3919 (ISSN-L)
- OpenAlex
- W2902677316
- Cited by
- 54
- References
- 79
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 13 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 4
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key R&D Program of China (Grant no. 2017YFA0505700)
- China Postdoctoral Science Foundation Funded Project (Grant no. 2018 T110950)
- Chongqing Science & Technology Commission (cstc2017jcyjA0207)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- olfactory bulb, depression, gut microbiota, microbiota-gut-brain axis, CACNA1E, CREB signaling, fecal microbiota transplantation, germ-free mice, brain-derived neurotrophic factor, CaMKII, nuclear receptor signaling, axonogenesis, major depressive disorder
- MeSH terms
- Gastrointestinal Microbiome, Animals, Depression, Gene Expression Regulation, Germ-Free Life, Olfactory Bulb, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Calcium Channels, R-Type, Cation Transport Proteins, Proteomics, Mice
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