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Although thermosonication (TS) treatment has been widely used in food sterilization, the viable but non-culturable (VBNC) of bacteria with TS treatment has still concerned potential food safety and public health. The molecular mechanism of VBNC status of bacteria with TS treatment is not clearly known. Therefore, in this study, we used Shewanella putrefaciens, which was a common putrefactive bacteria in aquatic products, to study the VBNC state of bacteria with TS treatment. Firstly, our results revealed that S. putrefaciens still could enter the VBNC state after TS treatments: 50 kHz, 300 W, 30 min ultrasonic treatment and 70 °C heating; Subsequently, we found the VBNC state of S. putrefaciens can resist the damage of TS treatment, such as cell wall break, DNA degradation, etc; Finally, four-dimensional data-independent acquisition-based proteomics showed that under VBNC state, S. putrefaciens upregulated functional proteins to resist TS treatment, such as: ribosomal proteins to accelerate the synthesis of stress proteins to counteract TS treatments, ornithine decarboxylase SpeF and MraY to repair TS treatment-induced damage, etc. Meanwhile, S. putrefaciens downregulates metabolic and transport functional proteins such as dehydrogenase to reduce the metabolism. Importantly, among those proteins, the ribosomal transcriptional regulatory protein family, such as rpsB, etc, may be the key proteins for S. putrefaciens entering VBNC state. This finding can provide some new strategies for preventing VBNC status of bacteria with TS treatment, such as: inhibition of key proteins, etc.
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Alcohol dependence is a chronic, relapsing encephalopathy characterized by compulsive craving for alcohol, loss of control over alcohol use, and the presence of negative emotions and physical discomfort when alcohol is unavailable. Harmful use of alcohol is one of the greatest risk factors for death, illness, and disability. Rho kinase inhibitors have neuroprotective effects. This study used metabonomics analysis to assess untreated astrocytes, astrocytes exposed to 75 mmol/L of alcohol, and astrocytes exposed to 75 mmol/L of alcohol and treated with 15 µg/mL fasudil for 24 h. One of the clearest differences between the alcohol-exposed and fasudil-treated alcohol-exposed groups was the abundance of lipids and lipid-like molecules, although glycerophospholipid metabolism was comparable in both groups. Our findings show that fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, providing a new approach for preventing and treating alcohol dependence.
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Alcoholismo , Astrocitos , Humanos , Alcoholismo/complicaciones , Metabolismo de los Lípidos , Etanol/efectos adversos , MetabolómicaRESUMEN
Backgrounds: Many pieces of evidence demonstrated that there were close relationships between gut microbiota and depression. However, the specific molecular mechanisms were still unknown. Here, using targeted metabolomics, this study was conducted to explore the relationships between microbial metabolites in feces and neurotransmitters in prefrontal cortex of depressed mice. Methods: Chronic unpredictable mild stress (CUMS) model of depression was built in this study. Targeted liquid chromatography-mass spectrometry analysis was used to detect the microbial metabolites in feces and neurotransmitters in prefrontal cortex of mice. Both univariate and multivariate statistical analyses were applied to identify the differential microbial metabolites and neurotransmitters and explore relationships between them. Results: Ninety-eight differential microbial metabolites (mainly belonged to amino acids, fatty acids, and bile acids) and 11 differential neurotransmitters (belonged to tryptophan pathway, GABAergic pathway, and catecholaminergic pathway) were identified. Five affected amino acid-related metabolic pathways were found in depressed mice. The 19 differential microbial metabolites and 10 differential neurotransmitters were found to be significantly correlated with depressive-like behaviors. The two differential neurotransmitters (tyrosine and glutamate) and differential microbial metabolites belonged to amino acids had greater contributions to the overall correlations between microbial metabolites and neurotransmitters. In addition, the significantly decreased L-tyrosine as microbial metabolites and tyrosine as neurotransmitter had the significantly positive correlation (r = 0.681, p = 0.0009). Conclusions: These results indicated that CUMS-induced disturbances of microbial metabolites (especially amino acids) might affect the levels of neurotransmitters in prefrontal cortex and then caused the onset of depression. Our findings could broaden the understanding of how gut microbiota was involved in the onset of depression.
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Depresión , Microbioma Gastrointestinal , Aminoácidos , Animales , Depresión/etiología , Depresión/metabolismo , Modelos Animales de Enfermedad , Ratones , Neurotransmisores/análisis , Neurotransmisores/metabolismo , TirosinaRESUMEN
Objective: Although many works have been done, the objectively measured diagnostic biomarkers are not available. Thus, we conducted this study to identify potential biomarkers for objectively diagnosing depression and explore the role of gut microbiota in the onset of depression. Methods: Major depressive disorder (MDD) patients (n=56) and demographic data-matched healthy controls (HCs) (n=56) were included in this study. The gut microbiota in fecal samples and inflammation-related factors in serum were measured. Both univariate and multivariate statistical analyses were performed to identify the differential gut microbiota and inflammation-related factors. Results: Finally, 46 differential operational taxonomic units (OTUs) (60.9% OTUs belonging to Firmicutes) and ten differential inflammation-related factors were identified. Correlation analysis showed that there were significant correlations between 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and seven differential inflammation-related factors. Meanwhile, 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and five differential inflammation-related factors (adiponectin, apolipoprotein A1, alpha 1-antitrypsin, neutrophilicgranulocyte count/white blood cell count and basophil count) were significantly correlated to depression severity. A panel consisting of these five differential inflammation-related factors could effectively diagnose MDD patients from HCs. Conclusions: Our results suggested that Firmicutes, especially family Lachnospiraceae, might play a role in the onset of depression via affecting the inflammation levels of host, and these five differential inflammation-related factors could be potential biomarkers for objectively diagnosing MDD.
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Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Microbiota , Biomarcadores , Trastorno Depresivo Mayor/diagnóstico , Humanos , Inflamación/diagnósticoRESUMEN
OBJECTIVE: Hyperglycemia is often observed in the patients after acute stroke. This study aims to elucidate the potential effect and mechanism of hyperglycemia by screening microRNAs expression in intracerebral hemorrhage mice. METHODS: We employed the collagenase model of intracerebral hemorrhage. Twenty male C57BL/6 mice were used and randomly divided in normo- and hyperglycemic. The hyperglycemia was induced by intraperitoneally injection of 50% of Dextrose (8 mL/kg) 3 hours after intracerebral hemorrhage. The neurologic impairment was investigated by neurologic deficit scale. To study the specific mechanisms of hyperglycemia, microRNAs expression in perihematomal area was investigated by RNA sequencing. MicroRNAs expression in hyperglycemic intracerebral hemorrhage animals were compared normoglycemic mice. Functional annotation analysis was used to indicate potential pathological pathway, underlying observed effects. Finally, polymerase chain reaction validation was administered. RESULTS: Intraperitoneal injection of dextrose significantly increased blood glucose level. That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals. A total of 73 differentially expressed microRNAs were identified via transcriptomics analysis. Bioinformatics analyses showed that these microRNAs were significantly altered in several signaling pathways, of which the hedgehog signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute intracerebral hemorrhage. Furthermore, polymerase chain reaction results validated the correlation between microRNAs and hedgehog signaling pathway. CONCLUSIONS: MicroRNA elevated in hyperglycemia group may be involved in worsening the neurological function via inhibiting the hedgehog signaling, which provides a novel molecular physiological mechanism and lays the foundation for treatment of intracerebral hemorrhage.
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Proteínas Hedgehog , MicroARNs , Transducción de Señal , Transcriptoma , Animales , Hemorragia Cerebral/genética , Modelos Animales de Enfermedad , Glucosa/toxicidad , Proteínas Hedgehog/metabolismo , Hiperglucemia/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Transcriptoma/genéticaRESUMEN
BACKGROUND: Although many works have been conducted to explore the biomarkers for diagnosing major depressive disorder (MDD), the widely accepted biomarkers are still not identified. Thus, the combined application of serum metabolomics and fecal microbial communities was used to identify gut microbiota-derived inflammation-related serum metabolites as potential biomarkers for MDD. METHODS: MDD patients and healthy controls (HCs) were included in this study. Both serum samples and fecal samples were collected. The liquid chromatography mass spectrometry (LC-MS) was used to detect the metabolites in serum samples, and the 16S rRNA gene sequencing was used to analyze the gut microbiota compositions in fecal samples. RESULTS: Totally, 60 MDD patients and 60 HCs were recruited. The 24 differential serum metabolites were identified, and 10 of these were inflammation-related metabolites. Three significantly affected inflammation-related pathways were identified using differential metabolites. The 17 differential genera were identified, and 14 of these genera belonged to phyla Firmicutes. Four significantly affected inflammation-related pathways were identified using differential genera. Five inflammation-related metabolites (LysoPC(16:0), deoxycholic acid, docosahexaenoic acid, taurocholic acid and LysoPC(20:0)) were identified as potential biomarkers. These potential biomarkers had significant correlations with genera belonged to phyla Firmicutes. The panel consisting of these biomarkers could effectively distinguish MDD patients from HCs with an area under the curve (AUC) of 0.95 in training set and 0.92 in testing set. CONCLUSION: These findings suggested that the disturbance of phyla Firmicutes might be involved in the onset of depression by regulating host's inflammatory response, and these potential biomarkers could be useful for future investigating the objective methods for diagnosing MDD.
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Gliomas are the most common type of primary brain tumor, yet the prognosis for glioma patients remains poor. Mutations in the promoter region of the telomerase reverse transcriptase gene (TERTp) are associated with diagnosis and poor prognosis in gliomas. Here, we developed a precise and rapid Sanger sequencing assay to screen or TERTp mutations. We established the Sanger sequencing approach for the detection of TERTp mutations based on human glioma cell lines U251 and assessed the analytical validation by determining the accuracy, sensitivity, precision, and specificity. In our study, we verified the accuracy of Sanger sequencing by the real-time polymerase chain reaction method. Our data showed that TERTp mutations were detected at an analytical sensitivity of 10% per mutant. The precision and specificity validation also showed the desired results. In total, 147 glioma patients were investigated for TERTp mutations, and of each patient, clinical data and molecular characteristics were analyzed. We found that anaplastic oligodendroglioma had the highest frequency of TERTp mutations (66.7%). No differences in TERTp mutation frequency were observed between frozen tissue specimens and formalin-fixed and paraffin-embedded tissue. TERTp mutations were associated with older patients (≥45 years), whereas isocitrate dehydrogenase (IDH) mutations were inclined to a younger age (<45 years), frontal location, and pathologic stage II-III patients. IDH mutations were significantly associated with O6-methylguanine-DNA methyltransferase (MGMT) methylation (P = 0.003) and lower Ki-67 protein expression (P = 0.011). Moreover, MGMT methylation was enriched in IDH-mutant/TERTp-mutant gliomas, and Ki-67 protein expression was the highest in the IDH-wild type/TERTp-mutant group. Taken together, the findings of this study indicate the establishment of a rapid, precise, and practical Sanger sequencing technique for TERTp mutations in gliomas that may show promising results in clinical applications.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Glioma/genética , Mutación , Oligodendroglioma/genética , Telomerasa/genética , Adulto , Anciano , Línea Celular Tumoral , Humanos , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
Chronic social defeat stress (CSDS) is widely applied to study of depression in rodents. 10-day CSDS was a most commonly employed paradigm but with high resilience ratio (â¼30%), producing potential variation in depression-like behavioral symptoms. Whether prolonged period (21 days) of CSDS would promote less resilience and reduce behavioral variability remains unknown. We applied 10-day and 21-day CSDS paradigms to induce mouse model of depression and compared their resilience ratio and behavioral phenotypes. Mice under 21-day CSDS had significantly lower resilience ratio and greater changes in behavioral indicators relative to mice under 10-day CSDS. Behavioral indicators from 21-day CSDS paradigm had higher correlations and better prediction for susceptibility which indicating higher uniformity in behavioral phenotypes. Furthermore, a subset of behavioral indicators in 21-day CSDS had high prediction efficacy and should be first applied to screen susceptibility of CSDS. Thus, our study demonstrates that 21-day CSDS is a more robust paradigm inducing reliable depression-like behaviors relative to 10-day CSDS, and should be preferentially used in rodent studies of depression.
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Depresión/psicología , Resiliencia Psicológica , Derrota Social , Estrés Psicológico/psicología , Animales , Enfermedad Crónica , Masculino , Ratones , Ratones Endogámicos C57BL , FenotipoRESUMEN
BACKGROUND: Major depressive disorder (MDD) and suicide are two major health problems, but there are still no objective methods to diagnose MDD or suicidal ideation (SI). This study was conducted to identify potential biomarkers for diagnosing MDD patients with SI. METHODS: First-episode drug-naïve MDD patients with SI and demographics-matched healthy controls (HCs) were recruited. First-episode drug-naïve MDD patients without SI were also included. The serum lipids, C-reactive protein (CRP), transferring (TRSF), homocysteine (HCY) and alpha 1-antitrypsin (AAT) in serum were detected. The univariate and multivariate statistical analyses were used to identify and validate the potential biomarkers. RESULTS: The 86 HCs, 53 MDD patients with SI and 20 MDD patients without SI were included in this study. Four potential biomarkers were identified: AAT, TRSF, high-density lipoprotein cholesterol (HDLC), and apolipoprotein A1 (APOA1). After one month treatment, the levels of AAT and APOA1 were significantly improved. The panel consisting of these potential biomarkers had an excellent diagnostic performance, yielding an area under the ROC curve (AUC) of 0.994 and 0.990 in the training and testing set, respectively. Moreover, this panel could effectively distinguish MDD patients with SI from MDD patients without SI (AUC=0.928). CONCLUSION: These results showed that these potential biomarkers could facilitate the development of an objective method for diagnosing MDD patients with SI, and the decreased AAT levels in MDD patients might lead to the appearance of SI by resulting in the elevated inflammation.
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Both inflammatory processes and gut microbiota have been implicated in the pathophysiology of depressive disorders. The class B scavenger receptor CD36 is involved in the cytotoxicity associated with inflammation. However, its role in depression has not yet been examined. In this study, we investigated whether CD36 affects depression by modulating the microbiota-gut-inflammasome-brain axis. We used CD36-/- (knockout) mice subjected to chronic social defeat stress, and measured the expression of CD36 in these depressed mice and in patients with depression. The hippocampus of CD36-/- mice was used to investigate changes in the NLRP3 inflammasome signaling pathway. The 16S rRNA gene sequence-based approach was used to compare the cecal microbial communities in CD36-/- and WT mice. The CD36 deficiency in CD36-/- mice alleviated chronic stress-induced depression-like behaviors. CD36 was upregulated in depressed mice as well as in depressed patients. Furthermore, the NLRP3 inflammasome signaling pathway was downregulated in the hippocampus of CD36-/- mice. The Simpson Diversity Index revealed increased cecal bacterial alpha-diversity in the CD36-/- mice. Among genera, Bacteroides, Rikenella, and Alloprevotella were significantly more abundant in the CD36-/- mice, whereas Allobaculum was less abundant, consistent with the attenuated inflammation in the hippocampus of CD36-/- mice. Our findings suggest that CD36 deficiency changes the gut microbiota composition, which in turn may impact depressive-like behaviors by affecting the inflammasome pathway.
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Microbioma Gastrointestinal , Inflamasomas , Animales , Trastornos de las Plaquetas Sanguíneas , Depresión , Enfermedades Genéticas Congénitas , Humanos , Ratones , ARN Ribosómico 16SRESUMEN
BACKGROUND: In previous studies, our team examined the gut microbiota of healthy individuals and depressed patients using fecal microbiota transplantation of germ-free (GF) mice. Our results showed that depression-like and anxiety-like behavioral phenotypes of host mice were increased, but the molecular mechanism by which gut microbiota regulate host behavioral phenotypes is still unclear. METHODS: To investigate the molecular mechanism by which gut microbiota regulate host brain function, adult GF mice were colonized with fecal samples derived from healthy control (HC) individuals or patients with major depressive disorder (MDD). Transcriptomic profiling of hypothalamus samples was performed to detect differentially expressed genes (DEGs). qRT-PCR was used for validation experiments. RESULTS: Colonization germ-free (CGF) mice had 243 DEGs compared with GF mice. The most enriched KEGG pathways associated with upregulated genes were "protein digestion and absorption," "extracellular matrix (ECM)-receptor interaction," and "focal adhesion." MDD mice had 642 DEGs compared with HC mice. The most enriched KEGG pathways associated with upregulated genes in MDD mice were also "protein digestion and absorption," "ECM-receptor interaction," and "focal adhesion." Meanwhile, the most enriched KEGG pathway associated with downregulated genes in these mice was "oxidative phosphorylation," and genes related to this pathway were found to be highly correlated in PPI network analysis. CONCLUSION: In summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota and that inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.
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BACKGROUND: Depression is a highly prevalent mental illness that severely impacts the quality of life of affected individuals. Our recent studies demonstrated that diterpene ginkgolides (DG) have antidepressant effects in mice. However, the underlying molecular mechanisms remained much unclear. METHODS: In this study, we assessed the antidepressant effects of chronic DG therapy in rats by evaluating depression-related behaviors, we also examined potential side effects using biochemical indicators. Furthermore, we performed an in-depth molecular network analysis of gene-protein-metabolite interactions on the basis of metabolomics. RESULTS: Chronic DG treatment significantly ameliorated the depressive-like behavioral phenotype. Furthermore, the neurotrophin signaling-related NT3-TrkA and Ras-MAPK pathways may play an important role in the antidepressant effect of DG in the hippocampus. CONCLUSION: These findings provide novel insight into the mechanisms underlying the antidepressant action of DG, and should help advance the development of new therapeutic strategies for depression.
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Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Diterpenos/farmacología , Ginkgólidos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antidepresivos/administración & dosificación , Diterpenos/administración & dosificación , Ginkgólidos/administración & dosificación , Hipocampo/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
Major depressive disorder (MDD) is a prevalent and debilitating psychiatric mood disorder that lacks objective laboratory-based tests to support its diagnosis. A class of microRNAs (miRNAs) has been found to be centrally involved in regulating many molecular processes fundamental to central nervous system function. Among these miRNAs, miRNA-134 (miR-134) has been reported to be related to neurogenesis and synaptic plasticity. In this study, the hypothesis that plasma miR-134 can be used to diagnose MDD was tested. Perturbation of peripheral and central miR-134 in a depressive-like rat model was also examined. By reverse-transcription quantitative PCR, miR-134 was comparatively measured in a small set of plasma samples from MDD and healthy control (HC) subjects. To determine its diagnostic efficacy, plasma miR-134 levels were assessed in 100 MDD, 50 bipolar disorder (BD), 50 schizophrenic (SCZ), and 100 HC subjects. A chronic unpredictable mild stress (CUMS) rat model was also developed to evaluate miR-134 expression in plasma, hippocampus (HIP), prefrontal cortex (PFC), and olfactory bulb. We found that plasma miR-134 was significantly downregulated in MDD subjects. Diagnostically, plasma miR-134 levels could effectively distinguish MDD from HC with 79% sensitivity and 84% specificity, while distinguishing MDD from HC, BD, and SCZ subjects with 79% sensitivity and 76.5% specificity. Congruent with these clinical findings, CUMS significantly reduced miR-134 levels in the rat plasma, HIP, and PFC. Although limited by the relatively small sample size, these results demonstrated that plasma miR-134 displays potential ability as a biomarker for MDD.
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Trastorno Bipolar , MicroARN Circulante , Trastorno Depresivo Mayor , MicroARNs , Animales , Biomarcadores , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/genética , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/genética , MicroARNs/genética , RatasRESUMEN
Emerging evidence has shown the age-related changes in gut microbiota, but few studies were conducted to explore the effects of age on the gut microbiota in patients with major depressive disorder (MDD). This study was performed to identify the age-specific differential gut microbiota in MDD patients. In total, 70 MDD patients and 71 healthy controls (HCs) were recruited and divided into two groups: young group (age 18-29 years) and middle-aged group (age 30-59 years). The 16S rRNA gene sequences were extracted from the collected fecal samples. Finally, we found that the relative abundances of Firmicutes and Bacteroidetes were significantly decreased and increased, respectively, in young MDD patients as compared with young HCs, and the relative abundances of Bacteroidetes and Actinobacteria were significantly decreased and increased, respectively, in middle-aged MDD patients as compared with middle-aged HCs. Meanwhile, six and 25 differentially abundant bacterial taxa responsible for the differences between MDD patients (young and middle-aged, respectively) and their respective HCs were identified. Our results demonstrated that there were age-specific differential changes on gut microbiota composition in patients with MDD. Our findings would provide a novel perspective to uncover the pathogenesis underlying MDD.
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Envejecimiento , Bacterias/clasificación , Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Adolescente , Adulto , Estudios de Casos y Controles , Humanos , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Adulto JovenRESUMEN
Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first-line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side-effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Dl-3-n-butylphthalide (NBP) is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The aim of this study was to investigate the effect of NBP in a chronic social defeat stress model of depression and its underlying molecular mechanisms. Here, we examined depression-related behavior and performed a targeted metabolomics analysis. Real-time quantitative polymerase chain reaction and western blotting were used to examine key genes and proteins involved in energy metabolism and the AKT/cAMP response element-binding protein (CREB) signaling pathway. Our results reveal NBP attenuates stress-induced social deficits, anxiety-like behavior and despair behavior, and alters metabolite levels of glycolysis and tricarboxylic acid (TCA) cycle components. NBP affected gene expression of key enzymes of the TCA cycle, as well as protein expression of p-AKT and p-CREB. Our findings provide the first evidence showing that NBP can attenuate stress-induced behavioral deficits by modulating energy metabolism by regulating activation of the AKT/CREB signaling pathway.
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Trastorno Depresivo Mayor , Fármacos Neuroprotectores , Animales , Benzofuranos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Metabolismo Energético , Ratones , Fármacos Neuroprotectores/uso terapéutico , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Derrota SocialRESUMEN
Objectives: Lipid metabolism is closely associated with many important biological functions. Here, we conducted this study to explore the effects of gut microbiota on the lipid metabolism in the prefrontal cortex of mice. Methods: Germ-free (GF) mice, specific pathogen-free (SPF) and colonized GF (CGF) mice were used in this study. The open field test (OFT), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were conducted to assess the changes in general behavioral activity. The liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) was used to obtain the lipid metabolites. Both one-way analysis of variance (one-way ANOVA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to obtain the key differential lipid metabolites. Results: The behavioral tests showed that compared to SPF mice, GF mice had more center distance, more center time, less immobility time and less latency to familiar food. Meanwhile, 142 key differential lipid metabolites between SPF mice and GF mice were identified. These lipid metabolites mainly belonged to glycerophospholipids, glycerolipids, sphingolipids, and saccharolipids. The gut microbiota colonization did not reverse these changed behavioral phenotypes, but could restore 25 key differential lipid metabolites. Discussion: These results showed that the absence of gut microbiota could influence host behaviors and lipid metabolism. Our findings could provide original and valuable data for future studies to further investigate the microbiota-gut-brain axis.
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Conducta Animal , Microbioma Gastrointestinal/fisiología , Metabolismo de los Lípidos , Corteza Prefrontal/metabolismo , Animales , Ansiedad/metabolismo , Ansiedad/microbiología , Depresión/metabolismo , Depresión/microbiología , Masculino , Metabolómica , Ratones Endogámicos BALB C , Organismos Libres de Patógenos EspecíficosRESUMEN
Major depressive disorder (MDD) patients in different age ranges might have different urinary metabolic phenotypes, because age could significantly affect the physiological and psychological status of person. Therefore, it was very important to take age into consideration when studying MDD. Here, a dual platform metabolomic approach was performed to profile urine samples from young and middle-aged MDD patients. In total, 18 and 15 differential metabolites that separately discriminated young and middle-aged MDD patients, respectively, from their respective HC were identified. Only ten metabolites were significantly disturbed in both young and middle-aged MDD patients. Meanwhile, two different biomarker panels for diagnosing young and middle-aged MDD patients, respectively, were identified. Additionally, the TCA cycle was significantly affected in both young and middle-aged MDD patients, but the Glyoxylate and dicarboxylate metabolism and phenylalanine metabolism were only significantly affected in young and middle-aged MDD patients, respectively. Our results would be helpful for developing age-specific diagnostic method for MDD and further investigating the pathogenesis of this disease.
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Biomarcadores/orina , Trastorno Depresivo Mayor/orina , Adulto , Factores de Edad , Femenino , Humanos , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Adulto JovenRESUMEN
AIMS: The microbiota has a profound impact on host development and function. Axon guidance is essential for the formation of neural circuits and plays an important role in neurological diseases and behavioral disorders. However, the impact of the microbiota on axon guidance signaling is unclear. MAIN METHODS: Gnotobiotic models-germ free mice were applied to explore behavioral phenotypes and possible molecular mechanisms that were evaluated by Realtime-PCR and western blot analysis. Primary cultures of mouse cortical neurons were performed to demonstrate the role of Sema3A on NR1D1 expression. KEY FINDINGS: The results showed that the microbiota modulates host behavior, and that colonization is not sufficient to normalize behavioral alterations in germ-free (GF) mice. Five genes, Sema3A, Sema3E, EphB2, Slit3 and Robo1, were differentially expressed in GF and specific pathogen-free (SPF) mice. Furthermore, colonization did not completely reverse the differential expression, which was consistent with the behavioral phenotypes in colonization germ-free (CGF) mice. The transcript and protein levels of Sema3A, and of its membrane-bound co-receptor NRP1, were increased in GF mice. Interestingly, Sema3A inhibited the expression of NR1D1, which was blocked by a RhoA/ROCK pathway agonist in primary cortical neurons. The NR1D1 and ROCK2 expression levels were reduced in GF and CGF mice compared with SPF mice, consistent with the increased expression of Sema3A. SIGNIFICANCE: Our findings suggest that the microbiota regulates axon guidance signaling in the prefrontal cortex. Furthermore, this effect appears to involve the inhibition of NR1D1 expression by Sema3A through the RhoA/ROCK pathway.
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Ansiedad , Orientación del Axón/fisiología , Microbiota , Neuronas/metabolismo , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Semaforina-3A/metabolismo , Estrés Psicológico , Animales , Ansiedad/metabolismo , Ansiedad/microbiología , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos , Cultivo Primario de Células , Transducción de Señal , Organismos Libres de Patógenos Específicos , Estrés Psicológico/metabolismo , Estrés Psicológico/microbiologíaRESUMEN
Available data indicate that patients with depression and anxiety disorders are likely to be at greater risk for suicide. Therefore, it is important to correctly diagnose patients with depression and anxiety disorders. However, there are still no empirical laboratory methods to objectively diagnose these patients. In this study, the multiple metabolomics platforms were used to profile the urine samples from 32 healthy controls and 32 patients with depression and anxiety disorders for identifying differential metabolites and potential biomarkers. Then, 16 healthy controls and 16 patients with depression and anxiety disorders were used to independently validate the diagnostic performance of the identified biomarkers. Finally, a panel consisting of four biomarkers-N-methylnicotinamide, aminomalonic acid, azelaic acid and hippuric acid-was identified. This panel was capable of distinguishing patients with depression and anxiety disorders from healthy controls with an area under the receiver operating characteristic curve of 0.977 in the training set and 0.934 in the testing set. Meanwhile, we found that these identified differential metabolites were mainly involved in three metabolic pathways and five molecular and cellular functions. Our results could lay the groundwork for future developing a urine-based diagnostic method for patients with depression and anxiety disorders.
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Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/orina , Biomarcadores/orina , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/orina , Adulto , Estudios de Casos y Controles , China , Ácidos Dicarboxílicos/orina , Femenino , Cromatografía de Gases y Espectrometría de Masas , Hipuratos/orina , Humanos , Modelos Logísticos , Masculino , Malonatos/orina , Metabolómica , Niacinamida/análogos & derivados , Niacinamida/orina , Curva ROC , Adulto JovenRESUMEN
[This corrects the article DOI: 10.18632/oncotarget.23933.].