Identification of genes and pathways related to atherosclerosis comorbidity and depressive behavior via RNA-seq and bioinformation analysis in ApoE−/− mice

Zhou, Junjie; Zhang, Chunjie; Wu, Xingwang; Xie, Qi; Li, Lan; Chen, Ying; Yan, Hong‐Bin; Ren, Peiyu; Huang, Xi

doi:10.21037/atm.2019.11.118

Cited by 14 publications

(12 citation statements)

References 30 publications

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“…In our published paper, we demonstrated that ApoE −/− mice with a high-fat diet accelerated the formation of atherosclerosis and depression-like behavior changes. RNA-seq combined with bioinformatics analysis showed that inflammatory chemokine genes and related pathways are highly expressed in the prefrontal cortex and hippocampus regions of the atherosclerosis co-depression mice, but the detailed mechanisms affecting these genes and pathways need to be further studied ( Zhou et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE−/− Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis

Liao

et al. 2022

Front. Mol. Biosci.

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Background: The diagnosis, treatment, and prevention of atherosclerosis co-depression are poor, so it is urgent to explore new targets. Based on the “microbiota-gut-brain axis,” this study aimed to investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus regions and the characteristics of the gut microbiota in ApoE−/− mice with atherosclerosis co-depression.Methods: ApoE−/− mice (hyperlipid feeding combined with binding, HFB group, n = 14, male) fed a high-fat diet for 16 weeks with binding stimulation were used as an animal model for atherosclerosis co-depression. The depression degree of mice was evaluated by body weight, sucrose preference test, open field test, and tail suspension test. Oil-red O staining, HE staining, and biochemical parameters were used to evaluate the damage degree of atherosclerosis in mice. LC-MS/MS technique for non-targeted lipidomics analysis was used to analyze the differential lipid metabolites in the prefrontal cortex and hippocampus regions of mice. 16S rDNA amplification sequencing was used to screen the differential gut microbial, and association analysis was performed with the differential lipid metabolites.Results: Compared with the normal control group (NC group), the HFB group showed depression-like behaviors and atherosclerosis-related pathological indicators. The differential lipid metabolites in the prefrontal cortex and hippocampus regions were mainly LPC, LPE, LPS, PC, PE, PS, PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and the retrograde endocannabinoid signaling pathway. At the same time, there were significant differences in the structure of the gut microbial community between the two groups. The abundance of Deferribacteres and Proteobacteria in the HFB group increased, while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level; the abundance of Desulfovibrio, Clostridium_IV, Helicobacter and Pseudoflavonifractor increased, while the abundance of Akkermansia decreased at the genus level.Conclusion: Atherosclerosis co-depression of ApoE−/− mice of the prefrontal cortex and hippocampus lipid metabolism pathways of disorder and the changes of to the gut microbiota, which leads to abnormal white matter and synaptic dysfunction, increased gut inflammation, and decreased gut permeability, leading to the release of inflammatory cytokines, there is a strong correlation between both, it further confirmed the existence of the “microbiota-gut-brain axis.”

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Section: Introductionmentioning

confidence: 99%

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE−/− Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis

Liao

et al. 2022

Front. Mol. Biosci.

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“…The aorta was opened lengthwise and the edges and corners were flattened on black boards. The en face analysis of the lesion area on the whole aorta was quantified based on Oil Red O staining, using Image-Pro Plus 6.0 software (Media Cybernetics, Bethesda, USA) [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Investigating the mechanisms of Modified Xiaoyaosan (tiaogan-liqi prescription) in suppressing the progression of atherosclerosis, by means of integrative pharmacology and experimental validation

Chen

Luo

Men

et al. 2021

Aging

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Atherosclerosis (AS)-related diseases remain among the leading causes of death worldwide. Modified Xiaoyaosan (also called Tiaogan-Liqi prescription, TGLQ), a traditional Chinese medical formulation, has been widely applied in the treatment of AS-related diseases. The aim of this study was to investigate the underlying pharmacological mechanisms of TGLQ in acting on AS. A total of 548 chemical compounds contained in TGLQ, and 969 putative targets, were collected from the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine, while 1005 therapeutic targets for the treatment of AS were obtained from the DisGeNET, TTD and CTD databases. Moreover, the 63 key targets were screened by the intersection of the targets above, and by network topological analysis. Further functional enrichment analysis showed that the key targets were significantly associated with regulation of the immune system and inflammation, improvement of lipid and glucose metabolism, regulation of the neuroendocrine system and anti-thrombosis effect. The in vivo experiments confirmed that TGLQ could reduce plasma lipid profiles and plasma inflammatory cytokines, and also inhibit AS plaque formation, within the AS model ApoE-/- mice. The in vitro experiments validated the hypothesis that TGLQ could significantly reduce intracellular lipid accumulation, suppress the production of inflammatory cytokines of macrophages induced by oxidized-LDL, and inhibit the protein expression of heat shock protein 90 and toll-like receptor 4. This study identified a list of key targets of TGLQ in the treatment of AS by applying an integrative pharmacology approach, which was validated by in vivo and in vitro experimentation.

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“…Depression is a mental illness associated with depressed mood, loss of interest, and energy fatigue ( Zhou et al, 2019 ). Not only it causes serious damage to the patients but also imposes a huge economic burden on society due to its high morbidity rate and recurrence rate ( Jun et al, 2014 ; Can et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Acupuncture Relieves Stress-Induced Depressive Behavior by Reducing Oxidative Stress and Neuroapoptosis in Rats

Cheng

Huang

et al. 2022

Front. Behav. Neurosci.

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Oxidative stress is closely related to the occurrence of depression. Acupuncture has been proved to be an effective method for treating depression. In order to explore the mechanism of the antidepressant effect of acupuncture, this study performed acupuncture prevention on chronic unpredictable mild stress (CUMS) depression model rats, and observed the effect of acupuncture on hippocampal oxidative stress and Nrf2 signaling pathway. Male SD rats were randomly divided into control group, CUMS group, acupuncture group, and fluoxetine group (n = 10/group). Fluoxetine, a common antidepressant, was used as a positive control drug in this study. In the fluoxetine group, rats were given fluoxetine (2.1 mg/kg) intragastrically once a day for 28 days. The acupoints of Shangxing (GV23) and Fengfu (GV16) were applied in acupuncture group, once every other day for 14 times in total. Behavioral tests and biological detections were used to evaluate the effects of the interventions and the changes of factors related to oxidative stress, Nrf2 pathway, and neuronal apoptosis. The results showed that both acupuncture and fluoxetine could increase sugar preference rate in SPT and decrease immobility time in FST in depression model rats. It also significantly decreased oxidative stress products such as ROS and H2O2, and elevated the protein and mRNA expressions of Nrf2 and HO-1. From Nissl’s staining, there were more abundant nerve cells in two intervention groups compared with CUMS group. Plus, acupuncture down-regulated the expression levels of Bax and caspase-3 and up-regulated the expression of Bcl-2. Our findings indicate that acupuncture improved depression-like behaviors of CUMS rats. And CUMS-induced depression-like behaviors in rats were related to oxidative stress and neuronal apoptosis in hippocampus. Acupuncture showed antidepressant effects in reducing oxidative stress products via regulating the Nrf2/HO-1 signaling pathway so that prevented neuronal apoptosis.

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Identification of genes and pathways related to atherosclerosis comorbidity and depressive behavior via RNA-seq and bioinformation analysis in ApoE−/− mice

Cited by 14 publications

References 30 publications

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE−/− Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE−/− Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis

Investigating the mechanisms of Modified Xiaoyaosan (tiaogan-liqi prescription) in suppressing the progression of atherosclerosis, by means of integrative pharmacology and experimental validation

Acupuncture Relieves Stress-Induced Depressive Behavior by Reducing Oxidative Stress and Neuroapoptosis in Rats

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