SCIENCE OF THE TOTAL ENVIRONMENT
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2022
·
IF 10.753
Tingting Zhou,Suli He,Xin Ye,Zhaolan Wei,Jian Wan,Hongmao Zhang,Shumao Ding
Multi-walled carbon nanotubes (MWCNTs) and dibutyl phthalate (DBP) exist extensively in the environment, and they are easy to form compound pollution through π-π interactions in the environment. We investigate whether DBP, an environmental hormone disruptor, mediated by CNTs can more easily cross the blood-brain barrier, and whether DBP entering the brain has neurotoxic effects on the cells in the brain. Experimental subjects were 40 male Kunming (KM) mice randomly divided into 4 groups: the control group; the MWCNTs group; the DBP group; and the MWCNTs+DBP group. The mice were exposed via tail intravenous injection once every 3 days for 21 days, following which toxicology studies were carried out. The results of behavioral experiments showed that the mice in the combined exposure group (MWCNTs+DBP) exhibited spatial learning and memory impairment, and anxiety-like behavior. Staining of hippocampal sections of mouse brain tissue showed that, in the CA1, CA2, and DG areas, the number of neurons decreased, the nucleus was pyknotic, the cell body was atrophied, and levels of the microglia marker Iba-1 increased. By proteomic KEGG analysis, we found that the DEPs were mainly those related to neurodegenerative diseases. Immunohistochemistry in the hippocampus indicated that the level of brain-derived neurotrophic factor (BDNF) in the DG region was significantly increased. RT-PCR results revealed that the expression levels of P53 , caspase3 , and Bax genes related to apoptosis were up-regulated. The experimental results demonstrated that the mechanism of the combined-exposure injury to neurons in the hippocampus of mice may be that MWCNTs with adsorbed DBP can induce the release of BDNF, accelerate the apoptosis of neurons, and reduce the number of nerve cells, which activates microglia, causing neuroinflammation and nervous system toxicity.
研究领域:
毒理学
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神经科学
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环境科学
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DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2024
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IF 10.3
Yunting Li,Anfei Liu,Kaiju Chen,Lifan Li,Xiaoshun Zhang,Fei Zou,Xingmei Zhang,Xiaojing Meng
Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the results of open field tests and Morris water maze tests demonstrated that chronic lead exposure caused learning and memory deficits and anxiety-like symptoms in mice. The serum butyric acid content of lead-treated mice decreased in a dose-dependent manner, and oral administration of butyrate significantly improved cognitive memory impairment and anxiety symptoms in lead-exposed mice. Moreover, butyrate alleviated neuroinflammation caused by lead exposure by inhibiting the STAT3 signaling in microglia. Butyrate also promoted the expression of acetyl-CoA synthetase ACSS2 in hippocampal neurons, thereby increasing the content of acetyl-CoA and restoring the expression of both histone H3K9ac and the downstream BDNF. We also found that the median butyric acid concentration in high-lead exposure humans was remarkably lower than that in the low-lead exposure humans (45.16 μg/L vs. 60.92 μg/L, P < 0.01), and that butyric acid significantly mediated the relationship of lead exposure with the Montreal cognitive assessment scores, with a contribution rate of 27.57 %. In conclusion, our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced neurotoxicity.
研究领域:
神经科学
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毒理学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2023
·
IF 4.7
Rongjun Liu,Daofan Sun,Xiuzhong Xing,Qingge Chen,Bo Lu,Bo Meng,Hui Yuan,Lan Mo,Liufang Sheng,Jinwei Zheng,Qiusheng Wang,Junping Chen,Xiaowei Chen
The comorbidity of pain and depression is frequently observed in patients suffering from chronic pain and depression. However, the comorbid mechanism is not well elucidated and the therapeutic medication is still inadequate. Oxytocin is a neuropeptide synthesized in the hypothalamus. It has been reported to relieve chronic pain and depressive symptoms. However, the analgesic action and mechanisms of oxytocin have mainly been investigated using peripheral or spinal administration. Because of the advantage of intranasal delivery of oxytocin in crossing the blood-brain barrier, we investigated the effect of intranasal application of oxytocin on neuropathic pain and comorbid depressive symptoms in both female and male mice. In female and male mice receiving spared nerve injury (SNI) surgery, intranasal oxytocin (2.4 μg, daily for 28 days) attenuated depression-like behavior , but did not alleviate mechanical hyperalgesia . Intranasal oxytocin not only inhibited the activation of microglia and astrocytes, but also increased the downregulated oxytocin receptor (OTR) expression, reversed the elevated GluN2A, and restored the decreased BDNF expression in the hippocampus . SNI also decreased OTR expression in the spinal cord and increased spinal GluN2A and BDNF. However, intranasal oxytocin treatment did not change the expression levels of OTR, GluN2A, or BDNF in the spinal cord of neuropathic mice. The results suggest that the oxytocin signaling in the hippocampus is involved in the comorbidity of pain and depression, and intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.
研究领域:
神经科学
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疼痛管理
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药理学
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行为科学
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DOI
PubMed
高影响因子
SOUTH AFRICAN JOURNAL OF BOTANY
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2025
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IF 2.7
Jingxin Chen,Jian Shi,Wenting Gu,Weiye Li,Ruiyin Lyu,Xueping Wu,Junming Wang,Chunhong Liu
Depression is a worldwide affliction that seriously compromises social adaptation and physical well-being. Citrus medica L. var. sarcodactylis Swingle (also known as Bergamot) is a citrus plant in the Rutanceae family. Bergamot essential oil, a naturally derived product, has been reported to possess neuroprotective effects. The present study aimed to reveal the neuroprotective mechanisms of bergamot essential oil in PC12 cells, and compare its efficacy with that of its predominant constituent, D-limonene. To confirm the target of action, this study sought to use PI3K inhibitor LY294002 to validate the mechanism in modulating autophagy and apoptosis of bergamot essential oil. By constructing a corticosterone-induced PC12 cell model of depression in vitro , we observed that bergamot essential oil stimulated the PI3K/AKT/mTOR signaling cascade, reducing autophagy markers LC3-II and p62 approximately by 22 % and 37 % respectively, and decreasing apoptosis rates by 37 %. Bergamot essential oil intervention also upregulated 5-HT levels and played a positive role in the BDNF/TrkB pathway which associated with synaptic plasticity. D-limonene (56.6 % of bergamot essential oil) was demonstrated to be a key contributor to these mechanisms. It exhibited protective effects comparable to bergamot essential oil against autophagy and BDNF/5-HT signaling activation, however, bergamot essential oil showed better efficacy in alleviating apoptosis. This study provides in vitro mechanistic evidence supporting the potential application of bergamot essential oil in the treatment of depression.
研究领域:
药理学
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神经科学
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植物学
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细胞生物学
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精神病学
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DOI
高影响因子
Brain Sciences
·
2025
·Vol. 15
·期 3
·236
·
IF 2.8
Xiaolin Fan,Hong Wang,Xiaoqiang Lv,Qi Wang,Boya Yu,Xiao Li,Liang Li,Yuhao Zhang,Ning Ma,Qing Lu,Airong Qian,Junhong Gao
Background: Blast traumatic brain injury (bTBI) can result in depression-like behaviors in the acute and chronic phases. SSRIs have been shown to significantly alleviate depression-like behaviors in animal models of traumatic brain injury (TBI) by increasing serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. However, the therapeutic effects of SSRIs on depression caused by bTBI remain unclear. Objective: Therefore, this study was aimed at investigating the therapeutic effects of SSRIs on depression-like behaviors in bTBI models. Methods: We created a rat model to study mild TBI by subjecting rats to increased blast overpressures (BOP) and injecting fluoxetine and escitalopram SSRIs intraperitoneally for 28 days. Results: On day 14 post-BOP exposure, rats treated with SSRIs showed decreased depression-like behaviors. This finding was accompanied by higher 5-HT levels in the hippocampus and increased numbers of Nestin-positive cells in the dentate gyrus. Furthermore, rats treated with SSRIs exhibited increased pCREB and BDNF protein expression in the hippocampus on days 7, 14, and 28 after bTBI. Conclusions: Overall, our findings indicate that SSRI-induced recovery from depression-like behaviors after mild bTBI is associated with the upregulation of 5-HT levels, pCREB and BDNF expression, and neurogenesis in the hippocampus.
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Ya-Nan Tang,Yun-Feng Bai,Ai Dong,Qin-Ling Rao,Hong-Hua Wu,Chun-Guo Wang,Yan-Tong Xu
Ethnopharmacological relevance Kai-Xin-San (KXS) is a classic prescription for treating affective disorders in traditional Chinese medicine (TCM) over millennium. Although antidepressant effects of KXS have been demonstrated in both clinical and preclinical studies, antidepressant constituents and action mechanisms of KXS remain unclear. Aim of the study To reveal antidepressant constituents and action mechanisms of KXS using the method of “fraction-spectrum-effect-mechanism”. Materials and methods Homologous fractions of KXS were isolated through solvent extraction combined with macroporous resin chromatography methods. The quantification of the fractions was performed using chemical chromogenic methods. Antidepressant effects of the homologous fractions were assessed using tail suspension test (TST), forced swimming test (FST) and open field test (OFT) in mice. Two major fractions of total phenols (TP) and total saponins (TS) were chosen for further studies. The constituents of TP and TS were identified using UPLC-Q-Exactive Orbitrap-MS (UPLC-MS) method, and their antidepressant effects were verified on chronic restraint stress (CRS) model in mice by behavioral evaluations including sucrose preference test (SPT), TST, FST and OFT. Network pharmacology was used to predict antidepressant mechanisms of TP and TS based on the homologous constituents determined in UPLC-MS analysis. Proteomic analyses were undertaken with tissues of hippocampus (HP) and prefrontal cortex (PFC) in CRS mice treated by TP and TS. Western blot (WB) was employed to verify the findings in network pharmacology and proteomic analyses. Results Five homologous fractions of essential oils (EO), TP, TS, oligosaccharides (OL) and polysaccharides (PO) were isolated from KXS with homologous contents exceeding 50 %. Results of TST and FST indicated that all the five fractions significantly decreased the immobility time of mice, while OFT results exhibited that their locomotor activities remained unchanged. A total of 50 constituents and 114 constituents were identified in the TP and TS, respectively. CRS tests demonstrated that both TP and TS significantly increased the percent of sucrose consumption and decreased the immobility time in the TST and FST, without affecting their locomotor activities. Results of both network pharmacology and proteomic analyses primarily pointed to similar contents highly related to depression. GO analysis on TP and TS principally enriched in synaptic structures and functions, as well as neural metabolic and gene expression processes. KEGG analysis on TP and TS principally enriched in pathways of neurodegeneration-multiple diseases, as well as neurotrophin signaling pathway in HP and PFC. Results of WB verified that TP and TS significantly reversed the decrease in signature proteins of synaptic plasticity including presynaptic SYN1, postsynaptic PSD95 and GRIA1, as well as the underlying mechanism of BDNF/TrkB/Akt pathway in the HP and PFC induced by CRS. Conclusion This is the first study on antidepressant constituents and action mechanisms of KXS guided by the method of “fraction-spectrum-effect-mechanism”. Albeit the findings are still preliminary, it provides an example in methodology for unraveling the complicated chemical system and action mechanisms of TCM prescriptions.
研究领域:
药理学
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神经科学
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民族药理学
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中医药学
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精神药理学
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蛋白质组学
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网络药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2023
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IF 5.1
Wu Yuhan,Zhu Zhanpeng,Lan Tian,Li Shuhan,Li Ye,Wang Changmin,Feng Yabo,Mao Xueqin,Yu Shuyan
Depression is a common psychological disease with high morbidity and mortality. Recently, the involvement of synaptic plasticity in the pathogenesis of depression has shed light on the direction of developing novel antidepressants. Levomilnacipran is a newly approved medication for the treatment of adult major depressive disorder. However, the detailed mechanisms underlying its antidepressant-like effects have yet to be illuminated. In this study, we aimed to investigate the role of levomilnacipran in regulating synaptic plasticity and explore the possible molecular mechanisms of its antidepressant effects using a rat model of depression induced by lipopolysaccharide (LPS). The results demonstrated that levomilnacipran (30 mg/kg, i.p.) significantly ameliorated depression-like behaviors in rats, alleviated the dysregulation of synaptic plasticity, and suppressed neuroinflammation within hippocampus induced by LPS-treatment. Levomilnacipran increased the expression of postsynaptic dense 95 (PSD-95) and synaptophysin (Syn) and reversed the imbalance between pro- and anti-inflammatory cytokines within hippocampus of depressed rats. Additionally, levomilnacipran elevated expression level of brain-derived neurotrophic factor (BDNF), accompanied by increased tyrosine kinase B (TrkB), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR). Taken together, these results suggest that levomilnacipran may exert antidepressant effects via upregulating BDNF/TrkB mediated PI3K/Akt/mTOR signaling pathway to improve synaptic plasticity. These findings reveal potential mechanisms for the antidepressant effects of levomilnacipran and offer new insights into the treatments for depression. Graphical Abstract
研究领域:
神经科学
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药理学
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分子生物学
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精神病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2019
·Vol. 10
·期 9
·6009-6019
·
IF 3.241
Yun Yu,Xiu-Yuan Lang,Xi-Xi Li,Run-Ze Gu,Qing-Shan Liu,Rongfeng Lan,Xiao-Yan Qin
The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2024
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IF 2.5
Xiyong Xiang,Siyu Xia,Shan Li,Yirong Zeng,Lixuan Wang,Yan Zhou
The occurrence and development of Alzheimer’s disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.
研究领域:
神经科学
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药理学
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分子生物学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2018
·Vol. 34
·期 1
·93-101
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IF 2.441
Zhu Ji-Xiao,Shan Jia-Ling,Hu Wei-Qiong,Zeng Jin-Xiang,Shu Ji-Cheng
Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally occurring polyphenolic compound. Previous study has shown that gallic acid possessed significant antidepressant-like activity in mice, which was partly mediated by increasing serotonin and catecholamine levels. The main aim of the present study is to investigate the possible effects of gallic acid on brain-derived neurotrophic factor (BDNF) signaling activation. Mice were exposed to chronic mild stress (CMS) and orally administrated with gallic acid for four weeks. The behavioral results showed that gallic acid not only reversed the decreased sucrose preference, but also attenuated the increased immobility time. In addition, gallic acid promoted both the BDNF and p-TrkB levels in the hippocampus induced by CMS. Moreover, the results also demonstrated that the inactivated Akt-mTOR signaling pathway, as well as its downstream effectors induced by CMS was activated again by gallic acid. Last, immunofluorescence detection indicated that gallic acid reversed the newborn neurons inhibition in the dentate gyrus by CMS. In conclusion, these results show that the activation of the hippocampal BDNF-Akt-mTOR signaling is involved in the antidepressant-like effects of gallic acid.
研究领域:
神经科学
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药理学
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压力研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Medicina-Lithuania
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2022
·Vol. 58
·期 12
·1749
·
IF 2.948
Aoqi Song,Zhenghua Wu,Wenjuan Zhao,Wenqing Shi,Ru Cheng,Jingjing Jiang,Zhuojun Ni,Han Qu,Xijier Qiaolongbatu,Guorong Fan,Yuefen Lou
Background and Objectives:Hypericum perforatum(HP) is widely used for depressive therapy. Nevertheless, the antidepressant effect and potential mechanism of hyperoside (Hyp), the main active component of HP, have not been determined. Materials and Methods: We performed ultra-performance liquid chromatography–quadrupole-time-of-flight–tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology to analyze the components in HP. Using data mining and network pharmacology methods, combined with Cytoscape v3.7.1 and other software, the active components, drug-disease targets, and key pathways of HP in the treatment of depression were evaluated. Finally, the antidepressant effects of Hyp and the mechanism involved were verified in chronic-stress-induced mice. Results: We identified 12 compounds from HP. Hyp, isoquercetin, and quercetin are the main active components of HP. The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), the Analysis Platform, DrugBank, and other databases were analyzed using data mining, and the results show that the active components of HP and depression are linked to targets such as TNF-, IL-2, TLR4, and so on. A potential signaling pathway that was most relevant to the antidepressant effects of Hyp is the C-type lectin receptor signaling pathway. Furthermore, the antidepressant effects of Hyp were examined, and it is verified for the first time that Hyp significantly alleviated depressive-like behaviors in chronic-stress-induced mice, which may be mediated by inhibiting the NLRP1 inflammasome through the CXCL1/CXCR2/BDNF signaling pathway. Conclusion: Hyp is one of the main active components of HP, and Hyp has antidepressant effects through the NLRP1 inflammasome, which may be connected with the CXCL1/CXCR2/BDNF signaling pathway.Keywords:depression;NLRP1 inflammasome;Hypericum perforatum;hyperoside;CXCL1/CXCR2;BDNF
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2026
·Vol. 14
·期 6
·e71912
·
IF 5
Yanni Wang,Zhaorong Yue,Manjie Xu,Wenjun Xu,Weizhong Zhang,Xiaolong Li,Qinghong Liu,Kailong Guan,Zewen Zhang,Yang Li,Xin Wang,Hongyu Li
Chinese Kushui Rose ( Rosa sertata × Rose rugosa ) is widely recognized for its medicinal and edible properties, and Chinese Kushui Rose Essential Oil (KREO) has attracted growing attention due to its potential anxiolytic and sedative-hypnotic effects. This study aims to systematically evaluate the preventive effects of KREO against depression-like behaviors and explore its underlying mechanisms. We identified 57 volatile compounds from KREO using gas chromatography–mass spectrometry (GC–MS), with the major constituents being citronellol, geraniol, and citronellyl acetate. In mice with chronic unpredictable mild stress (CUMS)-induced depression, administration of KREO facilitated body weight recovery, alleviated depressive-like behaviors, and improved voluntary locomotor activity and exploratory behavior. Mechanistic investigations revealed that KREO increased hippocampal levels of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF), reduced serum corticosterone (Cort) concentrations, and upregulated the expression of tyrosine receptor kinase B (TrkB) as well as the phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) in the hippocampus. Thus, KREO prevents depression-like behavior by enhancing monoaminergic neurotransmission and attenuating hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, with these effects associated with activation of the BDNF signaling pathway. These findings support the potential of KREO as a therapeutic intervention for depression and as a functional dietary ingredient.
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DOI
PubMed
高影响因子
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