Intestinal mRNA expression profile and bioinformatics analysis in a methamphetamine-induced mouse model of inflammatory bowel disease

Sun, Jiaxue; Chen, Fengrong; Chen, Cheng; Zhang, Zherui; Zhang, Zunyue; Tian, Wen; Yu, Juehua; Wang, Kunhua

doi:10.21037/atm-20-7741

Cited by 10 publications

(12 citation statements)

References 52 publications

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“…Proteomic changes in IBS Part of the challenge researchers face in understanding the pathophysiology of IBS results from its heterogeneity. In clinical biology, the use of mass spectrometry offers a means to interrogate the proteome of biological samples, such as blood, urine, saliva, or tissue, for the purpose of biomarker discovery (77). For instance, one study examined the urine proteome of women with IBS and subclassified each case on the basis of the predominant symptoms.…”

Section: Investigating the Mechanism Of Gut-brain Interactionmentioning

confidence: 99%

Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review

Tang¹,

Jiang²,

Wang³

et al. 2021

Ann Transl Med

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Objective: To improve the pathophysiological understanding of irritable bowel syndrome (IBS) by exploring the gut-brain axis.Background: Disorders of gut-brain interaction (DGBIs) are gastrointestinal (GI) disorders in which alterations in bowel functions occur. IBS, which is one of the most studied DGBIs, is linked with abdominal distress or pain without obvious structural or biochemical anomalies. Methods:The etiology of IBS has not been clearly described but is known to be multifactorial, involving GI motility changes, post-infectious reactivity, visceral hypersensitivity, gut-brain interactions, microbiota dysbiosis, small intestinal bacterial overgrowth, food sensitivity, carbohydrate malabsorption, and intestinal inflammation.Conclusions: One of the main features of IBS is the occurrence of structural and functional disruptions in the gut-brain axis, which alter reflective and perceptual nervous system reactions. Herein, we provide a brief summary of this topic. Furthermore, we discuss animal models, which are important in the study of IBS, especially as it is linked with stressors. These animal models cannot fully represent the human disease but serve as important tools for understanding this complicated disorder. In the future, technologies, such as organ-on-a-chip models and metabolomics, will provide novel information regarding the pathophysiology of IBS, which will play an important role in treatment development. Finally, we take a brief glance at how acupuncture treatments may hold potential for patients with IBS.

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Section: Investigating the Mechanism Of Gut-brain Interactionmentioning

confidence: 99%

Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review

Tang¹,

Jiang²,

Wang³

et al. 2021

Ann Transl Med

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“…The brain tissues were fixed in 4% paraformaldehyde (PFA) immediately after sacrifice. 2 H&E staining was performed on 5μm paraffin sections using standard H&E staining 2 protoccol which were described previously (Sun et al, 2020). The thin sections were made 2 with an ultramicrotome, stained by OsO 4 .…”

Section: Hande Staining and Electron Microscope Imagingmentioning

confidence: 99%

“…Sequencing libraries were prepared using the NEB Next Ultra RNA Library Prep Kit 1 (Illumina, USA), according to the manufacturer's recommendations, which were described 1 in our previous research (Sun et al, 2020). In brief, mRNA was purified using poly-T 1 oligo-attached magnetic beads, fragmentation was performed using divalent cations, and 1 library quality was assessed on the Agilent Bioanalyzer 2100 and qPCR.…”

Section: Rna Preparation Library Construction and Sequencingmentioning

confidence: 99%

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Quercetin ameliorates mitochondrial dysfunction and mitigates methamphetamine-induced anxiety-like behavior

Chen

Sun

Zhang

et al. 2021

Preprint

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Methamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression, during both MA use and withdrawal. Although numerous studies have reported an association between MA exposure and anxiety, the underlying mechanism remains elusive. In this study, escalating dose of MA was used to establish an MA-treated mouse model presenting anxiety behavior. RNA seq was then performed to profile the gene expression patterns in the hippocampus (HIPP). Differentially expressed genes (DEGs) were identified and function enrichment analysis was conducted to explore the underlying mechanisms. Quercetin as an mitochondria protector was used in vivo and in vitro. The C57BL/6J mice were co-treated with 50 mg/kg Quercetin and escalating MA. Anxiety behavior was evaluated by utilizing the elevated plus maze and the open field test. Transmission electron microscopy and immunohistochemistry were conducted to study the pathology of MA-inducced anxiety . The effects of MA and Quercetin on astrocytes were investigated by fluorescence staining, transmission electron microscopy, flow cytometry, and oxygen consumption rate. Western blot and qPCR were performed to analyze altered protein and gene levels of HIPP in mice and astrtocytes. The results demonstrated that forteen upregulated differentially expressed genes were identified and significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Interestingly, we found that quercetin was able to alleviate MA-induced anxiety-like behavior by improving neuron number and mitochondria injury. Mechanistically, quercetin can mitigate aberrant mitochondrial morphology and mitochondrial dysfunction not only by decreasing the levels of total cytoplasmic reactive oxygen species (ROS), mitochondria-derived ROS (mtROS), and mitochondrial membrane potential (MMP), but also increasing the oxygen consumption rate (OCR) and mitochondrial ATP production in vitro, indicating Quercetin ameliorated MA-induced anxiety-like behavior by modifying mitochondrial morphology and function. Furthermore, quercetin reversed OPA1 and DRP1 expression in astrocytes, and mitigated astrocyte activation and the release of inflammatory factors, which can trigger neuronal apoptosis and synaptic loss. Taken together, we provided evidence showing that MA can induce anxiety-like behavior via the induction of oxidative stress and mitochondrial dysfunction. Quercetin exerted antipsychotic activity through mitochondrial modulation, suggesting its potential for further therapeutic development in MA-induced anxiety.

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“…Beyond neuropsychiatric disorders, our previous studies showed that heroin abuse is often associated with decreased appetite, constipation, nutritional and gastrointestinal symptoms that can lead to low abstinence rate and malnutrition or nutritional risks during the withdrawal period (5)(6)(7). More seriously, drug-induced intestinal barrier lesions and severe enterogenic infections or related death were observed in Rhesus monkeys (5) and methamphetamine treated mice (8). Notably, lower zona occludens-1 (ZO-1) immune positivity was observed in heroin abusers compared to healthy controls (9), indicating that heroin affects the molecular integrity of tight junction (TJ) proteins, which correlates with gastrointestinal symptoms.…”

Section: Introductionmentioning

confidence: 99%

The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence

et al. 2021

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The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

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Intestinal mRNA expression profile and bioinformatics analysis in a methamphetamine-induced mouse model of inflammatory bowel disease

Cited by 10 publications

References 52 publications

Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review

Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review

Quercetin ameliorates mitochondrial dysfunction and mitigates methamphetamine-induced anxiety-like behavior

The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence

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