scholarly journals Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice

2022 ◽  
Vol 14 ◽  
Author(s):  
Lanxiang Liu ◽  
Haiyang Wang ◽  
Xueyi Chen ◽  
Yangdong Zhang ◽  
Wenxia Li ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Differentially Expressed ◽  
Messenger Rnas ◽  
Major Depressive ◽  
Epigenetic Biomarkers ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
Gut Microbiota Dysbiosis

Major depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls were detected, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level, and in further to explore the microbial-regulated pathological mechanisms of depression. As a result, 200 mRNAs, 358 lncRNAs, and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differential mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting these differential mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, a microbial-regulated lncRNA–miRNA–mRNA network based on RNA–RNA interactions was constructed. Subsequently, according to the competitive endogenous RNAs (ceRNA) hypothesis and the biological functions of these intersected genes, two neurodevelopmental ceRNA sub-networks implicating in depression were identified, one including two lncRNAs (4930417H01Rik and AI480526), one miRNA (mmu-miR-883b-3p) and two mRNAs (Adcy1 and Nr4a2), and the other including six lncRNAs (5930412G12Rik, 6430628N08Rik, A530013C23Rik, A930007I19Rik, Gm15489, and Gm16251), one miRNA (mmu-miR-377-3p) and three mRNAs (Six4, Stx16, and Ube3a), and these molecules could be recognized as potential genetic and epigenetic biomarkers in microbial-associated depression. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.

Modulation of gut microbiota by chlorogenic acid pretreatment on rats with adrenocorticotropic hormone induced depression-like behavior

2019 ◽  
Vol 10 (5) ◽  
pp. 2947-2957 ◽  
Author(s):  
Jing Song ◽  
Nian Zhou ◽  
Weini Ma ◽  
Xinyi Gu ◽  
Baizhang Chen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Mental Disorders ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Chlorogenic Acid ◽  
Adrenocorticotropic Hormone ◽  
Acid Pretreatment ◽  
Major Depressive ◽  
Vital Element ◽  
Gut Microbiota Dysbiosis

Gut microbiota dysbiosis has been implicated as a vital element in the development or exacerbation of mental disorders, such as major depressive disorder (MDD).

scholarly journals Investigating the convergent mechanisms between Major Depressive Disorder and Parkinson’s disease

2020 ◽  
Author(s):  
Angela A Tran ◽  
Myra De Smet ◽  
Gary D. Grant ◽  
Tien K. Khoo ◽  
Dean L Pountney
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cell Activation ◽  
Glutamate Excitotoxicity ◽  
Major Depressive ◽  
Glial Cell Activation ◽  
Underlying Mechanisms ◽  
The Brain

Major depressive disorder (MDD) affects more than cognition, having a temporal relationship with neuroinflammatory pathways of Parkinson’s disease (PD). Although this association is supported by epidemiological and clinical studies, the underlying mechanisms are unclear. Microglia and astrocytes play crucial roles in the pathophysiology of both MDD and PD. In PD, these cells can be activated by misfolded forms of the protein α-synuclein to release cytokines that can interact with multiple different physiological processes to produce depressive symptoms, including monoamine transport and availability, the hypothalamus-pituitary axis, and neurogenesis. In MDD, glial cell activation can be induced by peripheral inflammatory agents that cross the blood brain barrier and/or c-Fos signaling from neurons. The resulting neuroinflammation can cause neurodegeneration due to oxidative stress and glutamate excitotoxicity, contributing to PD pathology. Astrocytes are another major link due to their recognised role in the glymphatic clearance mechanism. Research suggesting that MDD causes astrocytic destruction or structural atrophy highlight the possibility that accumulation of α-synuclein in the brain is facilitated as the brain cannot adequately clear the protein aggregates. This review examines research into the overlapping pathophysiology of MDD and PD with particular focus on the roles of glial cells and neuroinflammation.

Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder

2016 ◽  
Vol 202 ◽  
pp. 254-257 ◽  
Author(s):  
Emiko Aizawa ◽  
Hirokazu Tsuji ◽  
Takashi Asahara ◽  
Takuya Takahashi ◽  
Toshiya Teraishi ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Major Depressive

scholarly journals SIGIRR and TNFAIP3 Are Differentially Expressed in Both PBMC and TNF-α Secreting Cells of Patients With Major Depressive Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Chin-Chuen Lin ◽  
Tiao-Lai Huang
Keyword(s):  
Immune Response ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Innate Immune ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Negative Regulators ◽  
Major Depressive ◽  
Tnf Α

Background: Major depressive disorder (MDD) is associated with the activation of the immune/inflammatory system. TNF-α is associated with MDD and poor treatment response. Toll-like receptors (TLR) are responsible in innate immune response, and is associated with MDD and antidepressant response. Some negative regulators of TLR pathway such as SOCS1, TOLLIP, SIGIRR, TNFAIP3, and MyD88s, are reported to be differentially expressed in the peripheral blood samples of patients of MDD.Methods: We recruited patients with MDD and healthy controls, collect their demographic data, and measured their mRNA levels of negative TLR regulators, using peripheral blood mononuclear cells (PBMC) and isolated TNF-α secreting cells. Clinical symptoms were evaluated using Halmiton Depression Rating Scale (Ham-D). Some patients were evaluated again after 4 weeks of antidepressant treatment.Results: Forty-seven patients with MDD and 52 healthy controls were recruited. Between the PBMC samples of 37 MDD patients and 42 controls, mRNA levels of SOCS1, SIGIRR, TNFAIP3, and MyD88s were significantly different. Between TNF-α secreting cells of 10 MDD patients and 10 controls, mRNA levels of SIGIRR and TNFAIP3 were significantly different. Change of Ham-D score only correlated significantly with TOLLIP mRNA level after treatment.Conclusion: SIGIRR and TNFAIP3, two negative regulators of TLR immune response pathways, were differentially expressed in both PBMC and TNF-α secreting cells of patients with MDD as compared to healthy controls. The negative regulations of innate immune response could contribute to the underlying mechanism of MDD.

scholarly journals Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

2020 ◽  
Author(s):  
Tingting An ◽  
Zhenhua Song ◽  
Jin-Hui Wang
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Molecular Mechanism ◽  
Chronic Stress ◽  
Medial Prefrontal Cortex ◽  
Differentially Expressed ◽  
Mild Stress ◽  
Major Depressive ◽  
Differentially Expressed Mirnas

Abstract Background Major depressive disorder (MDD) is a disease that seriously endangers human health and mental state. Chronic stress and lack of reward may reduce the function of the brain's reward circuits, leading to major depressive disorder. The effect of reward treatment on chronic stress-induced depression-like behaviors and its molecular mechanism in the brain remain unclear.Methods Mice were divided into the groups of control, chronic unpredictable mild stress (CUMS), and CUMS-companion. Mice of CUMS group was performed by CUMS for 4 weeks, and CUMS-companion group was treated by CUMS accompanied with companion. The tests of sucrose preference, Y-maze, and forced swimming were conducted to assess depression-like behaviors or resilience. High-throughput sequencing was used to analyze mRNA and miRNA profiles in the medial prefrontal cortex harvested from control, CUMS-MDD (mice with depression-like behaviors in CUMS group), Reward-MDD (mice with depression-like behaviors in CUMS-companion group), CUMS-resilience (resilient mice in CUMS group), Reward-resilience (resilient mice in CUMS-companion group) mice.Results The results provided evidence that accompanying with companion ameliorated CUMS-induced depression-like behaviors in mice. 45 differentially expressed genes (DEGs) are associated with depression-like behaviors, 8 DEGs are associated with resilience and 59 DEGs are associated with nature reward (companion) were identified. Furthermore, 196 differentially expressed miRNAs were found to be associated with companion. Based on the differentially expressed miRNAs and DEGs data, miRNA-mRNA network was established to be associated with companion.Conclusion Taken together, our data here provided a method to ameliorate depression-like behaviors, and numerous potential drug targets for the prevention or treatment of depression.

scholarly journals Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Javier R. Caso ◽  
Karina S. MacDowell ◽  
Ana González-Pinto ◽  
Saínza García ◽  
Javier de Diego-Adeliño ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Relative Abundance ◽  
Control Mechanisms ◽  
Major Depressive ◽  
Immune Pathways ◽  
Oxide Synthase ◽  
A Current ◽  
Inducible Nitric Oxide

AbstractAlthough alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.

Analysis of gut microbiota and intestinal integrity markers of inpatients with major depressive disorder

2021 ◽  
Vol 106 ◽  
pp. 110076 ◽  
Author(s):  
Paweł Liśkiewicz ◽  
Mariusz Kaczmarczyk ◽  
Błażej Misiak ◽  
Michał Wroński ◽  
Agata Bąba-Kubiś ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Major Depressive ◽  
Intestinal Integrity

scholarly journals Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Zhenhuang Zhuang ◽  
Ruotong Yang ◽  
Wenxiu Wang ◽  
Lu Qi ◽  
Tao Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Major Depressive Disorder ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Lower Risk ◽  
Neuropsychiatric Disorders ◽  
Microbiota Composition ◽  
Major Depressive ◽  
Gut Microbiota Composition

Abstract Background Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer’s disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ). Methods A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively. Results We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79–0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92–1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00–1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83–0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00–1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02–1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition. Conclusions These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.

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