BIOMEDICAL CHROMATOGRAPHY
·
2015
·Vol. 29
·期 11
·1737-1743
·
IF 1.723
Xue-jia Zhai,Fen Chen,Chao-ran Zhu,Yong-ning Lu
Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25–12,800 ng mL −1 with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group ( n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
生物化学
·
医学研究
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
·
2025
·
IF 2.5
Haohao Wang,Jinxiang Wu,Pan Wang,Wei Wang,Leilei Gao,Dong Liu,Xiaoyuan Ding,Ting Su
This study aims to investigate the pathogenesis of depression in mice using the chronic unpredictable mild stress (CUMS) model, with a particular focus on the changes in inflammatory gene networks and inflammatory factor levels under the condition of gut microbiota dysbiosis. The results indicate that CUMS-induced mice exhibited significant depressive-like behaviors. Specifically, they displayed reduced sucrose intake in the sucrose preference test, decreased central area distance and time in the open field test, and reduced percentage of entries and time spent in the open arm in the elevated plus maze test. Molecular biological analysis indicated that CUMS treatment significantly upregulated the levels of inflammatory factors TNF-α, IL-1β, IL-6, and IFN-γ in the serum and hippocampus of mice. Through high-throughput sequencing and Pearson correlation analysis, it was found that the levels of inflammatory factors were significantly positively correlated with the expression of multiple inflammatory pathway genes, as well as the abundance of beneficial and harmful bacteria. Furthermore, the persistent changes in inflammatory factors ultimately led to neuronal cell death. This study provides strong evidence for the role of disrupted “microbiota-gut-brain” axis homeostasis in the pathogenesis of CUMS-induced depression in mice. This finding offers a new perspective for understanding the pathological mechanisms of depression and provides strategies for future depression treatment.
研究领域:
神经生物学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
·
2025
·
IF 2.5
Yikai Chen,Wen Ye,Wenxin Wang,Nan Miao,Yongqiang Sha,Tao Sun
Major depressive disorder (MDD) is characterized by anhedonia and cognitive deficits. In this study, we investigated the therapeutic effects of nicotinic acid (NA), a nicotinamide adenine dinucleotide + (NAD + ) precursor, in a mouse chronic restraint stress (CRS) model. Behavioral assessments revealed that NA ameliorated depressive-like behaviors, evidenced by restored sucrose preference and reduced immobility in forced swim and tail suspension tests, without affecting motor coordination in the rotarod test. Hippocampal transcriptomic analysis indicated that NA reversed stress-induced gene dysregulation, activated neuroprotective Wnt/β-catenin, cGMP–PKG, and cAMP pathways, and rescued lipid and porphyrin metabolism. In conclusion, NA likely exerts antidepressant effects by remodeling hippocampal gene networks to enhance synaptic plasticity and restore metabolic homeostasis. These findings highlight NA as a promising metabolic antidepressant and support the development of NAD + precursor–based potential therapies for mood disorders.
研究领域:
神经生物学
·
精神病学
·
分子药理学
·
代谢组学
·
转化医学
·
表观遗传学
·
神经内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Zibo Li,Ziyang Huang,Zhiyi Wang,Zhenzhen Guo,Baoying Wang,Yucheng Li,Erping Xu
Background: Chaihu Longgu Muli Decoction (CLM) is a classical herbal formula originally documented in Shang Han Lun. With an 1800-year clinical history, CLM remains widely prescribed for depression (“Yu Zheng” in Traditional Chinese Medicine theory). Emerging evidence suggests that chronic stress-induced depression is closely linked to lung cancer progression and metastasis. However, the therapeutic potential of CLM in this context remains unexplored.Methods: A lung cancer cell xenograft model combined with chronic unpredictable mild stress (CUMS) was used to evaluate the effect of CLM on lung cancer growth. Proteomic analysis was performed to explore the underlying mechanisms by which CLM alleviates CUMS-induced lung cancer progression. Western blot and qPCR were conducted to detect changes in Rap1/ERK-mediated epithelial-mesenchymal transition (EMT) progression. Finally, Rap1 agonists were utilized to determine the therapeutic mechanism of CLM on cortisol or corticosterone (Cort)-induced EMT progression in lung cancer cells and a mouse lung cancer model.Results: In our study, CUMS promoted lung cancer xenograft growth, increased the expression of the proliferation marker Ki67, and elevated serum Cort levels. CLM treatment not only alleviated CUMS-induced depression-like behaviors, but also suppressed stress-driven tumor growth. These effects were replicated in a urethane-induced lung cancer model combined with CUMS. Proteomic analysis revealed that CLM’s anti-tumor effects were associated with modulation of the Rap1 pathway. Mechanistically, CUMS downregulated Rap1GAP, activating Rap1 and subsequent ERK1/2 phosphorylation, thereby promoting EMT in lung cancer tissues. CLM effectively reversed these effects by inhibiting Rap1/ERK-mediated EMT. In vitro, CLM suppressed cortisol-induced migration, invasion, and EMT in lung cancer cells, and these effects were attenuated by Rap1 agonists. Furthermore, CLM inhibited Cort-induced EMT and depression-like behaviors in vivo, while Rap1 activation diminished CLM’s efficacy against Cort-driven tumor growth.Conclusion: These findings suggest that Rap1/ERK-mediated EMT is a hallmark of chronic stress-associated lung cancer progression. CLM exerts its therapeutic effects by targeting this pathway, offering a novel strategy to mitigate stress-aggravated oncogenesis.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
应激与疾病
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2023
·
IF 3.8
Lingyu Qin,Junming Wang,Xiaohui Wu,Lingling Song,Yueyue Zhang,Mingzhu Gong,Yanmei Wang,Bingyin Li
ABSTRACT Lonicera japonica flos (LJF) is a common clinical herb with outstanding medicinal and nutritional value. This study aimed to evaluate the antidepressant effects of LJF’s active extract and compound chlorogenic acid (CGA) around BDNF-TrkB pathway. The results showed that LJF extracts and CGA had significant antidepressant effects, and the antidepressant effects of different extracts of LJF was highly positively correlated with the content of CGA (FST, r = 0.998; TST, r = 0.934). Moreover, LJF-70% ethanolic extract and CGA improved CUMS induced depressive behavior, upregulated protein expression levels of BDNF and p -TrkB in the hippocampus, restored the damage of hippocampal neurons, and protect liver from damage. In summary, this study demonstrated for the first time that LJF-70% ethanolic extract was the active extract of LJF antidepressant and CGA was its active antidepressant compound, and the antidepressant mechanism mainly involved the upregulation of BDNF-TrkB signaling pathway in the hippocampus of mice.
研究领域:
药理学
·
神经科学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Yuan Nai-jun,Zhu Wen-jun,Ma Qing-yu,Huang Min-yi,Huo Rou-rou,She Kai-jie,Pan Jun-ping,Wang Ji-gang,Chen Jia-xu
Accumulating evidence shows that neuroinflammation substantially contributes to the pathology of depression, a severe psychiatric disease with an increasing prevalence worldwide. Although modulating microglial phenotypes is recognized as a promising therapeutic strategy, effective treatments are still lacking. Previous studies have shown that luteolin (LUT) has anti-inflammatory effects and confers benefits on chronic stress-induced depression. In this study, we investigated the molecular mechanisms by which LUT regulates the functional phenotypes of microglia in mice with depressive-like behaviors. Mice were exposed to chronic restraint stress (CRS) for 7 weeks, and were administered LUT (10, 30, 40 mg· kg −1 ·day −1 , i.g.) in the last 4 weeks. We showed that LUT administration significantly ameliorated depressive-like behaviors and decreased hippocampal inflammation. LUT administration induced pro-inflammatory microglia to undergo anti-inflammatory arginase (Arg)-1 + phenotypic polarization, which was associated with its antidepressant effects. Furthermore, we showed that LUT concentration-dependently increased the expression of PPARγ in LPS + ATP-treated microglia and the hippocampus of CRS-exposed mice, promoting the subsequent inhibition of the NLRP3 inflammasome. Molecular dynamics (MD) simulation and microscale thermophoresis (MST) analysis confirmed a direct interaction between LUT and peroxisome proliferator-activated receptor gamma (PPARγ). By using the PPARγ antagonist GW9662, we demonstrated that LUT-driven protection, both in vivo and in vitro, resulted from targeting PPARγ. First, LUT-induced Arg-1 + microglia were no longer detected when PPARγ was blocked. Next, LUT-mediated inhibition of the NLRP3 inflammasome and downregulation of pro-inflammatory cytokine production were reversed by the inhibition of PPARγ. Finally, the protective effects of LUT, which attenuated the microglial engulfment of synapses and prevented apparent synapse loss in the hippocampus of CRS-exposed mice, were eliminated by blocking PPARγ. In conclusion, this study showed that LUT ameliorates CRS-induced depressive-like behaviors by promoting the Arg-1 + microglial phenotype through a PPARγ-dependent mechanism, thereby alleviating microglial pro-inflammatory responses and reversing microglial phagocytosis-mediated synapse loss.
研究领域:
神经科学
·
药理学
·
精神病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AFFECTIVE DISORDERS
·
2024
·
IF 4.9
Aoqi Song,Ru Cheng,Jingjing Jiang,Han Qu,Zhenghua Wu,Feng Qian,Shuyu Shen,Liwen Zhang,Zhiyu Wang,Wenjuan Zhao,Yuefen Lou
Background The antidepressant effect of hyperoside (HYP), which is the main component of Hypericum perforatum , is not established. This study aimed to determine the effects of HYP on depression. Methods The antidepressant-like effect of HYP was studied in mice induced by chronic restraint stress (CRS). The effects of HYP on behavior, inflammation, neurotransmitters, gut microbiota, and short-chain fatty acids (SCFAs) were studied in CRS mice. Results HYP improved depressive-like behavior in mice induced by CRS. Nissl staining analysis showed that HYP improved neuronal damage in CRS mice. Western blot (WB) analysis showed that HYP increased the expression levels of BDNF and PSD95 in the hippocampus of CRS mice. The results of ELISA showed that HYP down-regulated the expression levels of IL-6, IL-1β, TNF-α, and CORT in the hippocampus, blood, and intestinal tissues of mice and up-regulated the expression levels of 5-HT and BDNF. Hematoxylin and eosin (HE) staining results indicate that HYP can improve the intestinal histopathological injury of CRS mice. The results of 16S rRNA demonstrated that HYP attenuated the dysbiosis of the gut microbiota of depressed mice, along with altering the concentration of SCFAs. Limitations In the present study, direct evidence that HYP improves depressive behaviors via gut microbiota and SCFAs is lacking, and only female mice were evaluated, which limits the understanding of the effects of HYP on both sexes. Conclusions HYP can improve CRS-induced depressive-like behaviors in mice, which is associated with regulating the gut microbiota and SCFAs concentration.
研究领域:
药理学
·
神经科学
·
微生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROGASTROENTEROLOGY AND MOTILITY
·
2022
·Vol. 35
·期 2
·e14488
·
IF 3.96
Mengjuan Lin,Guiying Hu,Baoping Yu
Background Hydrogen sulfide (H 2 S), an important endogenous gasotransmitter, is involved in the modulation of gastrointestinal motility, but whether it mediates the intestinal dysmotility in irritable bowel syndrome (IBS) is not known. This study explored the significance of cystathionine-β-synthase (CBS)/H 2 S signaling in stress-induced colonic dysmotility. Methods A rat model of IBS was established using chronic water avoidance stress (WAS). Colonic pathological alterations were detected histologically. Intestinal motility was determined by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was assessed using the visceromotor response (VMR) to colorectal distension (CRD). Real-time PCR, Western blotting, and immunostaining were performed to identify the expression of CBS in the colon. The contractions of distal colon were studied in an organ bath system and H 2 S content was measured by ELISA. The effects of SAM, a selective CBS activator, on colonic dysmotility were examined. MEK1 was tested as a potential upstream effector of CBS/H 2 S loss. Key Results After 10 days of WAS, the ITT was decreased and FWC was increased, and the VMR magnitude in response to CRD was enhanced. The colonic CBS expression and H 2 S levels were significantly declined in WAS-exposed rats, and the density of CBS-positive enteric neurons in the myenteric plexus in WAS-treated rats was lower than that in controls. SAM treatment relieved WAS-induced colonic hypermotility via increased H 2 S production. AZD6244, a selective inhibitor of MEK1, partially reversed CBS downregulation and colonic hypermotility in WAS-treated rats. Conclusions & Inferences Decreased CBS/H 2 S signaling through increased MEK1 signaling might be important in the pathogenesis of chronic stress-induced colonic hypermotility. SAM could be administered for disorders associated with intestinal hypermotility.
研究领域:
胃肠病学
·
神经胃肠病学
·
药理学
·
应激生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Jiuyan Zhang,Yuan Zhao,Ning Sun,Manyu Song,Yongping Chen,Lin Li,Hailin Cui,Haotian Yang,Chuqiao Wang,Haiyang Zhang,Honggang Fan
Chronic stress induction in immunosuppression and splenocyte apoptosis is commonly associated with increased susceptibility to various diseases. Lycopene (LYC) is a member of the carotenoid family with immune restoration and anti-apoptotic function. However, little is known about the mechanisms underlying the protective roles of LYC against spleen injury induced by chronic stress. Herein, male Wistar rats were undergoing chronic restraint stress and/or administered LYC (10 mg/kg) for 21 days. The effective model establishment was validated by open-field tests and levels of corticosterone in serum. Histopathological staining observation displayed that LYC could reduce chronic stress-induced spleen structure damage. Furthermore, LYC treatment significantly reduced the number of apoptotic-positive splenocytes caused by chronic stress via the death receptor apoptotic pathway. We detected the interleukin 4 and interferon γ levels in serum and spleen to determine the ratio of Th1 and Th2 and found that LYC can alleviate the immunosuppression induced by chronic stress. Notably, western blot and real-time polymerase chain reaction indicated that LYC can reduce the expression of the Notch-pathway-related proteins and mRNA in rats exposed to chronic stress. Further study of the potential mechanisms by adding the Notch pathway inhibitor DAPT revealed that LYC alleviates the structure damage, apoptosis, and immunosuppression caused by chronic stress via the suppression of the Notch pathway. Overall, this study presents a strong rationale to target LYC as a treatment strategy to relieve chronic stress-induced spleen injury.
研究领域:
免疫学
·
药理学
·
分子生物学
·
应激生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）