CHEMOSPHERE
·
2016
·
IF 3.698
Zheng Cao,Xu Yang,Haiyang Zhang,Haoran Wang,Wanyue Huang,Feibo Xu,Cuicui Zhuang,Xiaoguang Wang,Yanfei Li
Aluminum (Al) is present in the daily life of humans, and the incidence of Al contamination increased in recent years. Long-term excessive Al intake induces neuroinflammation and cognition impairment. Neuroinflammation alter density of dendritic spine, which, in turn, influence cognition function. However, it is unknown whether increased neuroinflammation is associated with altered density of dendritic spine in Al-treated rats. In the present study, AlCl 3 was orally administrated to rat at 50, 150 and 450 mg/kg for 90d. We examined the effects of AlCl 3 on the cognition function, density of dendritic spine in hippocampus of CA1 and DG region and the mRNA levels of IL-1β, IL-6, TNF-α, MHC II, CX3CL1 and BNDF in developing rat. These results showed exposure to AlCl 3 lead to increased mRNA levels of IL-1β, IL-6, TNF-α and MCH II, decreased mRNA levels of CX3CL1 and BDNF, decreased density of dendritic spine and impaired learning and memory in developing rat. Our results suggest AlCl 3 can induce neuroinflammation that may result in loss of spine, and thereby leads to learning and memory deficits.
研究领域:
神经科学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
NEUROREPORT
·
2013
·Vol. 24
·期 12
·682
·
IF 1.404
Wang Guohua,Cheng Yufang,Gong Meifang,Liang Baofang,Zhang Mingzi,Chen Yupin,Zhang Cong,Yuan Xin,Xu Jiangping
Unraveling the pathophysiological basis for the development of and recovery from depression is a unique challenge. Dendritic plasticity has been reported to be involved in the development of depression. We modeled an anxiety/depression-like phenotype by chronic corticosterone exposure in mice and reversed this anxiety/depression-like phenotype by long-term treatment with fluoxetine (FLX). Spine density in the hippocampus was detected by Golgi–Cox staining at five time points. The data showed that 35 days of corticosterone exposure led to a decrease in spine density in CA1, concomitant with the onset of depression. Following 25 days of treatment with FLX, the decrease in both the dendritic spine density in the hippocampus and the anxiety/depression-like phenotype induced by chronic corticosterone recovered to normal levels concomitantly. Interestingly, the total spine density changes are all mainly driven by changes in thin and stubby spines, not mushroom spines, following chronic corticosterone or FLX treatment. Our results suggest that the changes in dendritic spine density in the hippocampus may be one of the pathophysiological mechanisms underlying the development of and recovery from depression, and the neuronal plasticity of CA1 is first impaired during the development of depression.
研究领域:
神经科学
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精神医学
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DOI
PubMed
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2023
·
IF 1.6
Xuena Zhang,Jie Li
ObjectivesTo observe changes in actin and dendritic spines in the hippocampus after propofol anesthesia, and to evaluate the role of these changes in subsequent learning impairment in both young (3-month-old) and aged (20-month-old) male rats.MethodsThe shuttle box test was used to evaluate learning from 1, 3, 7, or 14 days after anesthesia. Both F-actin content and dendritic spines in the hippocampal CA1 region were observed using immunofluorescent staining and western blot assays.ResultsThe latency of the escape response was significantly prolonged until 7 days after anesthesia in the aged rats, and their learning curves were shifted. Dendritic spines were also decreased in the aged rats within 7 days after anesthesia, and F-actin content was significantly increased until 14 days after anesthesia.ConclusionsLearning was inhibited after propofol anesthesia, especially in aged rats. The over-polymerization of actin and subsequent reorganization of dendritic spines in the hippocampus may be responsible for this learning impairment. Our findings suggest that synaptic plasticity may be an underlying mechanism of perioperative neurocognitive disorders.
研究领域:
神经科学
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药理学
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认知科学
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产品关联
DOI
高影响因子
NEURON
·
2023
·
IF 16.2
Ning Cheng,Qiqi Dong,Zhen Zhang,Li Wang,Xiaojing Chen,Cheng Wang
Egocentric representations of external items are essential for spatial navigation and memory. Here, we explored the neural mechanisms underlying egocentric processing in the retrosplenial cortex (RSC), a pivotal area for memory and navigation. Using one-photon and two-photon calcium imaging, we identified egocentric tuning for environment boundaries in dendrites, spines, and somas of RSC neurons (egocentric boundary cells) in the open-field task. Dendrites with egocentric tuning tended to have similarly tuned spines. We further identified egocentric neurons representing landmarks in a virtual navigation task or remembered cue location in a goal-oriented task, respectively. These neurons formed an independent population with egocentric boundary cells, suggesting that dedicated neurons with microscopic clustering of functional inputs shaped egocentric boundary processing in RSC and that RSC adopted a labeled line code with distinct classes of egocentric neurons responsible for representing different items in specific behavioral contexts, which could lead to efficient and flexible computation.
研究领域:
神经科学
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认知神经生物学
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系统神经科学
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计算神经科学
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行为神经科学
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分子与细胞神经科学
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2024
·Vol. 21
·期 1
·1-18
·
IF 9.3
Su Xi,Wang Guanyu,Liu Senqi,Li Jinming,Shao Minglong,Yang Yongfeng,Song Meng,Han Yong,Li Wenqiang,Lv Luxian
Autophagy is crucial for synaptic plasticity and the architecture of dendritic spines. However, the role of autophagy in schizophrenia (SCZ) and the mechanisms through which it affects synaptic function remain unclear. In this study, we identified 995 single nucleotide polymorphisms (SNPs) across 19 autophagy-related genes that are associated with SCZ. Gene Set Enrichment Analysis (GSEA) of data from the Gene Expression Omnibus public database revealed defective autophagy in patients with SCZ. Using a maternal immune activation (MIA) rat model, we observed that autophagy was downregulated during the weaning period, and early-life activation of autophagy with rapamycin restored abnormal behaviors and electrophysiological deficits in adult rats. Additionally, inhibition of autophagy with 3-Methyladenine (3-MA) during the weaning period resulted in aberrant behaviors, abnormal electrophysiology, increased spine density, and reduced microglia-mediated synaptic pruning. Furthermore, 3-MA treatment significantly decreased the expression and synaptosomal content of complement, impaired the recognition of C3b and CR3, indicating that autophagy deficiency disrupts complement-mediated synaptic pruning. Our findings provide evidence for a significant association between SCZ and defective autophagy, highlighting a previously underappreciated role of autophagy in regulating the synaptic and behavioral deficits induced by MIA.
研究领域:
神经科学
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分子生物学
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行为科学
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遗传学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2020
·
IF 3.263
Min Chen,Qiu-Ping Zhang,Ji-Xiao Zhu,Jie Cheng,Qing Liu,Guang-Hui Xu,Cheng-Fu Li,Li-Tao Yi
It has been reported that liquiritin produced an antidepressant-like effect in rodents. However, little information is known regarding its antidepressant activity with the regulation of fibroblast growth factor 2 (FGF-2), a protein maintaining development and maturation of the nervous central system . Therefore, the aim of the present study was to investigate the underlying FGF-2 modulation involved in the antidepressant-like effects of liquiritin. In the present study, mice were orally administrated with liquiritin for 7 days prior to LPS injection. The depressive-like behaviors , levels of FGF-2, number of Iba1 positive cells, expression of proinflammatory cytokines and density of dendritic spines were evaluated. The results showed that liquiritin significantly ameliorated the depressive-like behaviors in mice response to LPS injection. Liquiritin reversed the reduction of FGF-2 levels in the hippocampus of LPS induced mice. In addition, the microglial activation caused by LPS was attenuated by liquiritin, in accordance with downregulation in mRNA levels of proinflammatory cytokines. Moreover, liquiritin also increased the density of dendritic spines in the hippocampus, which was suppressed by LPS. In conclusion, our findings demonstrated that liquiritin exerted the antidepressant-like effects in LPS-induced depression through FGF-2 enhancement by inhibiting neuroinflammation and maintaining synaptogenesis .
研究领域:
药理学
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神经科学
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免疫学
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DOI
PubMed
高影响因子
Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-20
·
IF 4.546
Yu Hui,Shao Shumin,Xu Junnan,Guo Haibiao,Zhong Zhangfeng,Xu Jiangping
Background Fresh or dried Persimmon leaves (Diospyros kaki Thunb.) exhibit preventive effects on cardiovascular and cerebrovascular diseases. However, their antidepressant effects and underlying mechanisms are unclear. Thus, we investigated mechanisms responsible for Persimmon leaf extract (PLE) activity on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice.Methods CSDS was used as a mouse model of depression. We performed the sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) to identify depressive-like behavior. Spine density and dendritic morphology were assessed using Golgi staining. Neurochemicals were quantified by microdialysis, doublecortin by immunofluorescence, and cAMP using an ELISA kit. Finally, the levels of cortical proteins of phosphorylated cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), postsynaptic density synapsin-1 and protein 95 (PSD95) were quantified by western blot. 16S rRNA gene sequencing was used to detect fecal microbiota.Results Treatment of CSDS-subjected mice with PLE (30.0–60.0 mg/kg, i.g.) enhanced sucrose preference, decreased immobility times in the TST and FST but did not affect locomotor activity. Furthermore, persistent social defeat stress decreased dendritic spine density and dendritic length in the brain, as well as decreased PSD95 and synapsin-1 expression. PLE, interestingly, inhibited dendritic spine loss and increased synaptic protein levels. PLE also increased brain levels of 5-HT, cAMP, phosphorylated (p)-CREB, BDNF, PSD95, and synapsin-1 in mice subjected to CSDS. Furthermore, PLE increased their doublecortin-positive cell count in the hippocampal dentate gyrus. CSDS mice represented a distinct fecal microbiota cluster which differed compared with normal C57BL/6J mice, and the phenotype was rescued by PLE.Conclusion sPLE alleviated CSDS-induced depressive behaviors and spinal damage by suppressing serotonin reuptake and activating the cAMP/CREB/BDNF signaling pathway. Simultaneously, PLE influenced the composition of the fecal microbiota in CSDS-subjected mice.
研究领域:
药理学
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神经科学
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行为科学
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微生物学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2019
·
IF 0.931
Zhi-Jun HE,Yang BAI,Qiong-Hui ZHAO,Pei OUYANG,Jia-Zuan NI,Qiong LIU,Wen-Biao GAN,Xue-Ji ZHANG
Alzheimer's disease (AD) is a major type of dementia in the elderly. Clinical medication at present can only relieve symptoms but has no therapeutical effect. Thus, it is urgent to develop an effective drug for the treatment of AD. In this study, 2-month-old triple transgenic AD model mice (3 × Tg-AD) was treated with 0.2 and 1.0 mM bis(ethylmaltolato) oxidovanadium IV (BEOV) in drinking water for 2 months respectively. The results of open field test, elevated plus-maze test and Y maze test showed that BEOV could significantly improve the exploratory ability, memory capacity and exercise ability and relieve the anxiety of 4-month-old 3 × Tg-AD mice. The dendritic spines of pyramidal neuron in neocortex were detected by in vivo two-photon imaging of YFP and AD-YFP mice (the offspring of 3 × Tg-AD and YFP mice). The numbers of dendritic spines increased in YFP mice but decreased in AD-YFP mice from 2.5-month-old to 3.5-month-old. Treatment with BEOV (1.0 mM) in the AD-YFP mice significantly increased the numbers of total dendritic spines, mushroom spines and thin spines, which suggested that BEOV could protect cortical neurons and reduce the loss of dendritic spines. The contents of metal ions in the brain of mice were further measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that BEOV (1.0 mM) could significantly increase the contents of V and Se and decrease the contents of Fe, Zn, Hg, Pb, Bi and Ni in AD brains, implying that vanadium might synergize with selenium to regulate the contents of metal ions in AD mice. Summarily, BEOV could mediate the homeostasis of multiple metal ions in AD brain and protect cortical neurons by reducing the loss of dendritic spines, thus to interfere with the pathological process of AD.
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
高影响因子
Chinese Medicine
·
2021
·Vol. 16
·期 1
·1-19
·
IF 5.455
Zhang Xian,You Lifang,Zhang Xiaohui,Wang Fangfang,Wang Yi,Zhou Jue,Liu Chang,Qu Fan
Background Chinese herbal medicine (CHM) has significant effects that improve the reproductive functions of patients with polycystic ovary syndrome (PCOS). However, the intergenerational effects of CHM on offspring and the underlying mechanism of CHM remain unclear. This study aimed to explore the effects and the underlying mechanism of CHM, specifically the Bu-Shen-Tian-Jing formula (BSTJF), on model rats with polycystic ovary syndrome (PCOS) and the neurobehavioral alterations of female offspring born to PCOS rats administered BSTJF.Methods High-performance liquid chromatography-mass spectrometry (HPLC–MS) and network pharmacology analysis were performed to identify the active ingredients and potential targets of BSTJF. Moreover, PCOS model rats were used to validate the role of BSTJF in reproduction and progeny neural development and to confirm the network pharmacological targets.Results A total of 91 constituents were characterized from BSTJF. The 20 most significant KEGG pathways and the high-frequency genes of these pathways were predicted to be putative targets of these molecules. The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. The target residence time of the 5-week-old female offspring of the BSTJF group was higher than that of the PCOS group in the water maze experiment. Compared to the PCOS group, the changes in dendritic spine density, ultrastructure of neurons and synapses, and Gabrb1 and Grin2b protein expression levels in the hippocampus of female offspring were partially reversed in the BSTJF group.Conclusion sBSTJF can effectively improve ovarian follicle development in PCOS rats and has positive effects on pubertal neurobehavioral alterations in the female offspring of these rats by reversing dendritic spine density, the ultrastructure of neurons and synapses, and the Gabrb1 and Grin2b protein expression levels in the hippocampus.
研究领域:
药理学
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生殖医学
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神经科学
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中医
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
·
IF 4.8
Zhiqiang Lu,Yuan Gao,Zhijie Bao,Songyi Lin
The peptide Ser-Phe-Gly-Asp-Ile (SFGDI), derived from sea cucumber, has demonstrated neuroprotective effects in cell models; however, the in vivo neuroprotective efficacy of SFGDI remains unexplored. In this study, we utilized a cognitive disorder mouse model induced by scopolamine and observed that daily oral administration of SFGDI at a dosage of 40 mg/kg resulted in improved behavioral performance in the Passive avoidance test, the Channel-type water maze test, and the Novel object recognition test (P < 0.05). Furthermore, our investigation into the underlying neuroprotective mechanisms of SFGDI revealed that it reduced oxidative stress levels through the activation of the Sirt3/SOD/ROS pathway, thereby balancing hippocampal unsaturated lipids (P < 0.05) in the mouse hippocampus. Moreover, SFGDI significantly decreased hippocampal neuroinflammation by modulating the activation of microglia and hypertrophy of astrocytes. Additionally, SFGDI was found to enhance synaptic plasticity in the mouse hippocampus by activating the ChAT/p-CaMKⅡ/BDNF pathway and increasing spine density in neuron cells (P < 0.05), particularly mushroom spines (P < 0.05). These experiments demonstrate that SFGDI exhibits neuroprotective effects by regulating hippocampal oxidative stress through the Sirt3/SOD/ROS pathway and synaptic plasticity via the ChAT/p-CaMKⅡ/BDNF pathway in the mouse hippocampus, thus emerging as a potential neuro-nutraceutical agent for alleviating memory impairment.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
NEUROPHARMACOLOGY
·
2022
·
IF 5.273
Jingli Chen,Chang Liu,Mu Xu,Jiaxi Zhu,Zhongyuan Xia
Chronic stress is associated with impairment of synapse plasticity in hippocampus and cognitive dysfunction in rodent and human. Notably, corticosterone (CORT) is believed to take responsibility for dendritic atrophy and reduction of spine number induced by chronic stress in hippocampus. But little is known about the molecular mechanisms underlying CORT induced abnormal synapse plasticity and cognitive dysfunction. Drebrin is an F-actin binding protein that modulates memory formation and maintenance by controlling the genesis and morphology of dendritic spines . In addition, miRNAs have been reported to participate in the negative regulation of protein-coding genes. In this study, five miRNAs capable of targeting Drebrin were selected by searching miRNA databases. One of these miRNAs, miR-19b-3p, was found to be upregulated in the hippocampal neurons of mice with chronic restraint stress (CRS). Luciferase reporter assay and Fluorescence in situ hybridization (FISH) were employed to identify the interaction between miR-19b-3p and Drebrin. In addition, silencing miR-19b-3p expression in vivo using an antagomir or in vitro using an inhibitor increased Drebrin expression , ameliorated the abnormal dendritic structure and upregulated the spine density in hippocampal CA1 pyramidal neurons of CRS mice and primary hippocampal neurons cultured under CORT stimulation, respectively. Electrophysiological analysis revealed that inhibition of miR-19b-3p rescued the limited synaptic transmission and synaptic plasticity in hippocampal neurons. Moreover, blocking miR-19b-3p drastically protected against cognitive deficits in CRS mice. These in vivo and in vitro findings indicate that the upregulation of miR-19b-3p exacerbates CRS-induced abnormal synaptic plasticity and cognitive impairment by targeting Drebrin.
研究领域:
神经科学
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分子生物学
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认知科学
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产品关联
DOI
PubMed
高影响因子
EMBO REPORTS
·
2022
·Vol. 23
·期 10
·e54543
·
IF 9.071
Xuanyue Ma,Liuren Li,Ziming Li,Zhengyi Huang,Yaorong Yang,Peng Liu,Daji Guo,Yueyao Li,Tianying Wu,Ruixiang Luo,Junyu Xu,Wen-Cai Ye,Bin Jiang,Lei Shi
Regulation of mRNA translation is essential for brain development and function. Translation elongation factor eEF2 acts as a molecular hub orchestrating various synaptic signals to protein synthesis control and participates in hippocampus-dependent cognitive functions. However, whether eEF2 regulates other behaviors in different brain regions has been unknown. Here, we construct a line of Eef2 heterozygous (HET) mice, which show a reduction in eEF2 and protein synthesis mainly in excitatory neurons of the prefrontal cortex. The mice also show lower spine density, reduced excitability, and AMPAR-mediated synaptic transmission in pyramidal neurons of the medial prefrontal cortex (mPFC). While HET mice exhibit normal learning and memory, they show defective social behavior and elevated anxiety. Knockdown of Eef2 in excitatory neurons of the mPFC specifically is sufficient to impair social novelty preference. Either chemogenetic activation of excitatory neurons in the mPFC or mPFC local infusion of the AMPAR potentiator PF-4778574 corrects the social novelty deficit of HET mice. Collectively, we identify a novel role for eEF2 in promoting prefrontal AMPAR-mediated synaptic transmission underlying social novelty behavior.
研究领域:
神经科学
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分子生物学
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行为科学
✓ 已验证
DOI
PubMed
高影响因子
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