NEUROREPORT
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2022
·
IF 1.703
Peng-Cheng Zhao,Zhen-Shan Huang,Shao-Nian Xu,Peng-Cheng Deng,Feng Qian,Jian Shi,Yong-Ming Zhang
To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Lei Wu,Wenqing Cheng,Haoke Xiang,Yaping Zhu,Yiran Jiang,Zixuan Wei,Mengqi Shao,Liyuan Tian,Yan Sun,Chao Lu
Chaihu Shugan San produces rapid antidepressant-like effects within 2 h in female CRS-exposed mice. • The rapid effect is comparable in onset to ketamine in female chronically stressed mice. • Hippocampal TC2N is a negative regulator of the rapid antidepressant-like action of CSS. • TC2N down-regulation is associated with hippocampal ERβ–eNOS–CaMKII–BDNF signaling. • The estrogen receptor β-linked mechanism was demonstrated in female mice and requires validation in males. Ethnopharmacological relevance Chaihu Shugan San (CSS), a classical seven-herb formula from the Ming-dynasty text Jing-Yue Quanshu, is widely prescribed for depressive disorders in China. Previous preclinical studies reported antidepressant-like effects only after weeks of repeated administration, mostly in male animals. Whether a single dose of CSS can produce rapid antidepressant-like effects in female animals, and through what mechanism, remains unclear. Aim of the study To determine whether a single administration of CSS produces rapid antidepressant-like effects in female mice exposed to chronic restraint stress (CRS), and to explore the underlying hippocampal mechanism. Methods and materials CSS quality was controlled by HPLC quantification of four index components. Female CRS mice received a single dose of CSS (1, 2 or 4 g/kg, i. g.) or ketamine (10 mg/kg, i. p.), followed by behavioral testing (tail suspension, forced swimming, sucrose preference and open field tests) within 2–24 h. Hippocampal RNA sequencing, RT-qPCR, Western blotting and ELISA were used to identify and validate candidate targets; hippocampal AAV-mediated TC2N overexpression and pretreatment with the ERβ antagonist acolbifene or the CaMKII inhibitor KN-93 were used for interventional validation. Results Batch-to-batch variation of the four index components was below 10% (RSDs 3.51–5.66%), with naringin (313.07 ± 11.16 μg/mL) and hesperidin (196.40 ± 11.11 μg/mL) as the major constituents. Acute administration of CSS (2 and 4 g/kg), like ketamine, shortened immobility time in the tail suspension test at 2 h and in the forced swimming test at 12 h, and restored sucrose preference at 24 h, without affecting locomotor activity. Hippocampal transcriptomics identified Tc2n as up-regulated by CRS and down-regulated by CSS, with Esr2, Nos3 and Camk2a showing the opposite pattern; these changes were confirmed at the mRNA and protein levels within 2 h. Hippocampal TC2N overexpression or pretreatment with acolbifene or KN-93 abolished the rapid behavioral effects of CSS and the associated changes in ERβ–eNOS–CaMKII–BDNF signaling. Conclusion CSS produces rapid, ketamine-comparable antidepressant-like behavioral effects in female CRS-exposed mice, accompanied by down-regulation of hippocampal TC2N and involvement of ERβ, eNOS, CaMKII and BDNF. Because only female mice were studied, these findings are specific to females and support an estrogen-linked mechanism that warrants confirmation in male animals and further translational study. Download: Download high-res image (318KB) Download: Download full-size image
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DOI
高影响因子
Frontiers in Neuroscience
·
2025
·
IF 3.2
Mengjie He,Mengying Hu,Tingqiao Wang,Zeping Zuo,Hongkai Li,Zhiwei Zhao,Yunwen Hao,Xueling Dai,Jianfang Wang,Yaxuan Sun
Background: In recent years, depression has become a global public health concern, and one of the common concomitant symptoms are diminished sexual motivation and impaired sexual performance. The aim of this study was to investigate the potential effects of Morinda officinalis oligosaccharides (MOO) on depression and its concomitant symptom, sexual dysfunction.Methods: Chronic unpredictable mild stress (CUMS)-induced depression model was constructed, and the effects of MOO on depression and sexual abilities were evaluated.Results: The results revealed that MOO was able to alleviate CUMS-induced depression-like behavior in mice, to inhibit hippocampal neuron apoptosis, to reverse monoamine neurotransmitter imbalance, increase Brain-derived neurotrophic factor (BDNF) expression levels in the hippocampus, to modulate the composition and distribution of gut microbiota, and to increase the abundance of probiotics after continuous gavage of MOO for 28 days. MOO further confirmed that sexual dysfunction is closely related to the development of depression by improving the lack of sexual motivation and low sexual performance in CUMS-induced depressed mice, modulating the disruption of sex hormone secretion in serum, and alleviating sperm morphology and functional defects in the epididymis.Conclusion: These findings on MOO provide a basis for exploring its antidepressant mechanism, its use to improve hypogonadotropic symptoms, and for future development of new antidepressant drug to improves hypogonadotropic symptoms.
研究领域:
神经科学
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药理学
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心理学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Chen Juanli,Wei Chuanfei,Zhang Yingchao,Chen Qingfa,Li Xuemei,Zhang Wei,Zhang Xiaoping,Han Fabin
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) plaques, leading to neuronal death. Notably, there are no therapeutically efficacious treatments for this disorder. This study investigates the neuroprotective mechanisms of curcumin. In vitro experiments demonstrated that curcumin significantly promoted the proliferation of neural stem cells (NSCs) derived from E16 mouse embryos. Additionally, in the APP/PS1 transgenic mouse model, curcumin improved cognitive function, as evidenced by a shorter escape latency and increased platform crossing frequency in the Morris water maze test and enhanced novel object recognition. Histological analysis showed that curcumin reduced Aβ accumulation in the hippocampal and cortical regions. Molecular studies revealed that curcumin upregulated the expression of BDNF and enhanced phosphorylation of CREB. Collectively, these findings indicate that curcumin exerts neuroprotective effects through multiple mechanisms, including promoting NSC proliferation, reducing Aβ accumulation, and the potential modulation of the BDNF-CREB signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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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
TOXICOLOGY
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2024
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IF 4.8
Linjing Xu,Huan Liu,Yifeng Rang,Lizi Zhou,Xukai wang,Yinhuan Li,Chunhong Liu
Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.
研究领域:
毒理学
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神经科学
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药理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chai Yuhui,Cai Yawen,Fu Yu,Wang Yingdi,Zhang Yiming,Zhang Xue,Zhu Lingpeng,Miao Mingxing,Yan Tianhua
Depression is a common and serious mental disorder. Data on its pathogenesis remain unclear and the options of drug treatments are limited. Here, we explored the role of pyroptosis, a novel pro-inflammatory programmed cell death process, in depression as well as the anti-depression effects and mechanisms of salidroside (Sal), a bioactive extract from Rhodiola rosea L. We established a corticosterone (CORT)-induced or lipopolysaccharide (LPS)-induced mice in vivo, and CORT, or nigericin (NLRP3 agonist)-induced PC12 cells in vitro. Our findings demonstrated that Sal profoundly mediated CORT or LPS-induced depressive behavior and improved synaptic plasticity by upregulating the expression of brain-derived neurotrophic factor (BDNF) gene. The data showed upregulation of proteins associated with NLRP3-mediated pyroptosis, including NLRP3, cleaved Caspase-1, IL-1β, IL-18, and cleaved GSDMD. The molecular docking simulation predicted that Sal would interact with P2X7 of the P2X7/NF-κB/NLRP3 signaling pathway. In addition, our findings showed that the NLRP3-mediated pyroptosis was regulated by P2X7/NF-κB/NLRP3 signaling pathway. Interestingly, Sal was shown to ameliorate depression via suppression of the P2X7/NF-κB/NLRP3 mediated pyroptosis, and rescued nigericin-induced pyroptosis in the PC12 cells. Besides, knock down of the NLRP3 gene by siRNA markedly increased the inhibitory effects of Sal on pyroptosis and proinflammatory responses. Taken together, our findings demonstrated that pyroptosis plays a crucial role in depression, and Sal ameliorates depression by suppressing the P2X7/NF-κB/NLRP3-mediated pyroptosis. Thus, our study provides new insights into the potential treatment options for depression.
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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免疫学
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精神病学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2022
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IF 5.318
Jingru Zheng,Yuanhong Gao,Jie Ding,Na Sun,Songyi Lin
The study aims to investigate the repair effects of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) and Ser-Asn-Val-Phe-Asp-Met-Phe (SNVFDMF) peptides on scopolamine-caused memory impairment in mice. Behavioral experiments have revealed that Antarctic krill peptides can ameliorate scopolamine caused memory impairment by changing the behavior of mice. In comparison with the scopolamine group, the two peptides at a dose of 40 mg/kg could improve memory impairment. The serum SOD activity (82.82 ± 0.19 vs 79.47 ± 2.42 U/mg prot) and hippocampal ACh level (101.46 ± 3.23 vs 99.85 ± 7.13 μg/mg prot) of SSDAFFPFR were higher than those of SNVFDMF. Hippocampal AChE activity (0.20 ± 0.03 vs 0.53 ± 0.02 U/mg prot), hippocampal MDA level (1.56 ± 0.01 vs 1.63 ± 0.05 nmol/mg prot) and the serum MDA level (3.38 ± 0.24 vs 3.88 ± 0.21 nmol/mg prot) was lower than that of SNVFDMF. The state of mouse hippocampal cells was further observed by a microscopic imaging system. In addition, western blot analysis showed that SSDAFFPFR could significantly inhibit the expression of Bax, caspase-3, and p53, and promote the expression of BCL-XL, CREB, and BDNF, thus protecting hippocampal neurons in mice. In conclusion, the Antarctic krill peptide can repair scopolamine-induced memory impairment in mice.
研究领域:
神经科学
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药理学
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生物化学
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产品关联
DOI
高影响因子
Theranostics
·
2020
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IF 8.579
Teng Ma,Yafeng Yang,Xin Quan,Lei Lu,Bing Xia,Jianbo Gao,Fengyu Qi,Shengyou Li,Laihe Zhao,Liangwei Mei,Yi Zheng,Yanbing Shen,Zhuojing Luo,Yan Jin,Jinghui Huang
Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo . The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro , enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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DOI
PubMed
高影响因子
Journal of Essential Oil Bearing Plants
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2024
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IF 2.1
Minghui Tang,Yong Ai,Ni Song,Xian Xu,Lin Geng,Dongqiu Chen,Lu Ren,Xiaolu Chen,Jingyi Chen,Lanyue Zhang,Tinggang He
The antidepressant-like effects of five herbal essential oils (EOs), Jasminum sambac (Linn.) Aiton essential oil (JSEOs), Magnolia denudata Desr. essential oil (MDEOs), Rosa rugosa Thunb. essential oil (RREOs), Aloysia citriodora Ortega ex Pers. essential oil (ACEOs) and Abies balsamea (L.) Mill. essential oil (ABEOs) were evaluated. By virtue of a reserpine-induced depression mouse model, the antidepression activities and mechanisms of these EOs were explored. The results indicated that the inhalation of EOs significantly ameliorated depression-like behaviors in reserpine-induced depression mice, including a decrease in anxiety and immobility time. JSEOs and ABEOs significantly attenuated reserpine-induced depression-like behaviors, particularly the decreased body weight and immobility time, as determined by tail suspension and forced swimming tests. Furthermore, RT-qPCR and western blotting analyses indicated that the EOs influenced brain-derived neurotrophic factor (BDNF), serotonin1A (5-HT1A), and inflammatory cytokine levels. ACEOs attenuated reserpine-induced hippocampal and neuronal damage, significantly increased glucocorticoid receptor (GR) and 5-HT1A levels, and suppressed the inflammatory response. These results provide new insights into the antidepressant effects of herbal EOs and suggest that the five EOs evaluated in this study are potential nutraceuticals for the treatment of depression.
研究领域:
药理学
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神经科学
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DOI
高影响因子
Food Science & Nutrition
·
2021
·Vol. 9
·期 7
·3722-3731
·
IF 2.863
Lin Zhu,Yingjuan Liu,Xiaolin Wu,Yuqian Ren,Qinghua Zhang,Leiming Ren,Yunliang Guo
Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo , CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.
研究领域:
神经科学
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衰老研究
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2023
·
IF 13.6
Weiwei Wang,Xin Li,Qiuhui Qian,Jin Yan,Haishan Huang,Xuedong Wang,Huili Wang
Because triclosan (TCS) has been confirmed to cause severe neurotoxicity, it is urgent to disclose the underlying toxicity mechanisms at varying levels. TCS exposure resulted in a series of malformations in larval zebrafish, including reduced neurons, blood-vessel ablation and abnormal neurobehavior. Apoptosis staining and the upregulated expression of proapoptotic genes demonstrated that TCS induced neuronal apoptosis and neurotransmitter disorders. By integrating RT-qPCR analysis with the effects of pathway inhibitors and agonists, we found that TCS triggered abnormal regulation of neuron development-related functional genes, and suppressed the BDNF/TrkB signaling pathway. TCS inhibited total m 6 A-RNA modification level by activating the demethylase ALKBH5, and induced neurodevelopmental toxicity based on the knockdown experiments of alkbh5 and molecular docking . The main novelties of this study lies in: (1) based on specific staining and transgenic lines, the differential neurotoxicity effects of TCS were unravelled at individual, physiological, biochemical and molecular levels in vivo ; (2) from a epigenetics viewpoint, the decreasing m 6 A methylation level was confirmed to be mediated by alkbh5 upregulation; and (3) both homology modeling and molecular docking evidenced the targeting action of TCS on ALKBH5 enzyme. These findings open a novel avene for TCS’s risk assessment and early intervention of the contaminant-sourcing diseases.
研究领域:
毒理学
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神经科学
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分子生物学
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表观遗传学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
·
2019
·Vol. 35
·期 4
·661-672
·
IF 4.246
Li Yang,Liu Jing,Liu Xu,Su Cun-Jin,Zhang Qi-Lin,Wang Zhi-Hong,Cao Lei-Fang,Guo Xue-Yan,Huang Ya,Luo Weifeng,Liu Tong
The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naïve and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression.
研究领域:
神经科学
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精神病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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