TOXICOLOGY LETTERS
·
2020
·
IF 3.569
Meng Shi,Shikun Deng,Yalan Cui,Xuejun Chen,Tong Shi,Liangcai Song,Ruihua Zhang,Yi Zhang,Jianfu Xu,Jingjing Shi,Chen Wang,Liqin Li
Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4×LD 50 (16.8 μg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly ( p < 0.05) longer while the crossing times were significantly decreased in the Morris water task ( p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 ± 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 ± 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure.
研究领域:
神经科学
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毒理学
·
生物化学
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DOI
高影响因子
Heliyon
·
2023
·
IF 4
Shuang Peng,Xuling Wu,Qian Zheng,Jianwei Xu,Dongjun Xie,Mengyun Zhou,Mingwei Wang,Yongran Cheng,Lan Ye,Xiangang Mo,Zhanhui Feng
Seizure is associated with pathological changes of hippocampus, but the mechanism by which hippocampal neuronal apoptosis promotes epilepsy is unclear. Our previous study showed that the expression of NHE-1 was increased in epileptic model rats. Therefore, this study further explores the effect of NHE-1 on hippocampal cells apoptosis and seizure in lithium chloride-pilocarpine epileptic model rats. First, we established a lithium chloride-pilocarpine induced epileptic rat model and detected the expression of NHE-1, calpain1 and apoptosis in the hippocampus. Then, we further down-regulated NHE-1 to observe the expression of calpain1 and apoptosis in the hippocampus, as well as its effect on seizures in rats. We found that the expression of NHE-1 and calpain1 and apoptosis in the hippocampus was significant increased in the model group. After down-regulating NHE-1, the expression of calpain1 was decreased, and hippocampal cell apoptosis was alleviated. In addition, down-regulation of NHE-1 reduced the frequency and duration of seizures in epileptic rats. Therefore, hippocampal NHE-1 overexpression is closely related to the development of neuronal apoptosis in a rat model of epilepsy, and downregulating NHE-1 expression can reduce cell apoptosis. Moreover, the NHE-1/calpain1 signaling pathway may be an important mechanism leading to hippocampal cell apoptosis.
研究领域:
神经科学
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分子生物学
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DOI
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Xiaorong Wu,Shiqi Li,Meijia Zhang,Shengjun Bai,Yangyue Ni,Qiaoqiao Xu,Yun Fan,Chuncheng Lu,Zhipeng Xu,Chenbo Ji,Guizhen Du,Yufeng Qin
Bisphenol AP (BPAP), a structural analog of bisphenol A (BPA), has been widely detected in environment and biota. BPAP was reported to interfere with hormone and metabolism, while limited data were available about its effects on neurobehavior, especially exposure to it during early-life time. A mouse model of early-life BPAP exposure was established to evaluate the long-term neurobehaviors in offspring . Collectively, early-life BPAP exposure caused anxiety-like behaviors and impaired learning and memory in adult offspring. Through brain bulk RNA-sequencing (RNA-seq), we found differential expressed genes were enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, single-nucleus RNA-sequencing (snRNA-seq) showed BPAP exposure altered the transcriptome of microglia in hippocampus. Mechanistically, BPAP exposure induced inflammations in hippocampus through upregulating Iba-1 and activating the microglia. In addition, we observed that BPAP exposure could activate peripheral immunity and promote proportion of macrophages and activation of dendritic cells in the offspring. In conclusion, early-life exposure to BPAP impaired neurobehaviors in adult offspring accompanied with excessive activation of hippocampal microglia. Our findings provide new clues to the underlying mechanisms of BPAP's neurotoxic effects and therefore more cautions should be taken about BPAP.
研究领域:
毒理学
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
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2025
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IF 5.8
Gu Yuang,Yao Yu,Lou Qiuwen,Zhu Xinyan,Lan Ju,Gao Chenshu,Wu Shuangshuang,Liang Jingjia,Xu Cenglin,Wang Yi,Cheng Heming,Chen Zhong
Epilepsy is one of the most prevalent and severe neurological disorders, and it is inadequately controlled with currently available medications. While cinnabar (mercury(II) sulfide)—a traditional Chinese medicine—has historical application in epilepsy treatment, its therapeutic efficacy and underlying mechanisms are unclear. In this study, we find that cinnabar exerts model-dependent antiseizure efficacy in mice. Specifically, it significantly attenuates acute seizures, enhances the termination of diazepam-resistant status epilepticus, and reduces spontaneous seizures in the kainic acid (KA)-induced seizure model. Conversely, no therapeutic effect was found in the maximal electroshock-, pentylenetetrazole-, or kindling-induced seizure model. Fiber photometry revealed that cinnabar normalizes KA-induced hippocampal neurotransmission imbalances by simultaneously decreasing glutamate hyperactivity and γ-aminobutyric acid hypoactivity. Furthermore, cinnabar has neuroprotective effects and alleviates comorbid anxiety-like behaviors, while showing no alterations in motor function. Our findings suggest cinnabar's potential as a therapeutic agent for seizure management, via a mechanism associated with the reversal of the hippocampal excitatory/inhibitory imbalance.
研究领域:
神经病学
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药理学
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分子神经科学
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转化医学
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药物毒理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 17
·4282
·
IF 4.183
Yunfeng Zhou,Xue Tao,Zhi Wang,Li Feng,Lisha Wang,Xinmin Liu,Ruile Pan,Yonghong Liao,Qi Chang
An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.Keywords:olfactory bulbectomy;depression;hippocampus;metabonomics;autophagy
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
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IF 7.1
Enhui He,Shengwei Xu,Guihua Xiao,Yuchuan Dai,Xinrong Li,Yilin Song,Fei Gao,Yu Zhang,Shihong Xu,Xinxia Cai
The acute hippocampal slice is useful for understanding how epilepsy spatially initiates, propagates, and terminates in the hippocampus, which is vital to study the epileptic mechanism in it. However, it is challenging to detect the electrical signals of the main cell layer (the granular cell layer in the dentate gyrus (DG) and the pyramidal cell layer in CA1 and CA3a–c), which play an important role in epilepsy, because it is difficult to be accurately located by electrodes and typically show low throughput. In this study, a special in vitro microelectrode array (MEA) for rat hippocampal slices was fabricated. The recording sites of the MEA were designed along the main cell layer to record accurately the electrical signals of this layer in each hippocampal sub-region. A special “less-hydrophilic-MWCNTs/PEDOT:PSS modification method” for in vitro MEA was applied to deposit electrochemically the MWCNTs/PEDOT:PSS nanocomposites onto the surface of the microelectrodes, which significantly improved their performance with low impedance (36.41 ± 3.07 kΩ), small phase delay (−41.2 ± 4.90°), high signal-to-noise ratio (S/N = 5.4) and good biocompatibility. The application of high-K + -ACSF and D-AP5 (NMDA receptor antagonist) showed a neural signal projection pathway of the epileptic discharges in the hippocampal slice. The epileptic discharges originated in CA3b, where the neurons acted as a pacemaker, and spread to CA1 and DG bi-directionally along the main cell layer. Moreover, the epileptic discharges spread backward (CA3b to DG) faster than forward (CA3b to CA1). The MEA provides a reliable and sensitive dedicated biosensor for hippocampal slices.
研究领域:
神经科学
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生物医学工程
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产品关联
DOI
高影响因子
CEREBRAL CORTEX
·
2023
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IF 3.7
Wan Changjian,Song Xueqing,Zhang Zhuyu,Hu Wenxiang,Chen Yanhua,Sun Wei,Liu Zhibin,Wang Songhua,Meng Wei
Physical exercise has been shown to have an impact on memory and hippocampal function across different age groups. Nevertheless, the influence and mechanisms underlying how voluntary exercise during puberty affects memory are still inadequately comprehended. This research aims to examine the impacts of self-initiated physical activity throughout adolescence on spatial memory. Developing mice were exposed to a 4-wk voluntary wheel running exercise protocol, commencing at the age of 30 d. After engaging in voluntary wheel running exercise during development, there was an enhancement in spatial memory. Moreover, hippocampal dentate gyrus and CA3 neurons rather than CA1 neurons exhibited an increase in the miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents. In addition, there was an increase in the expression of NR2A/NR2B subunits of N-methyl-D-aspartate receptors and α1GABAA subunit of gamma-aminobutyric acid type A receptors, as well as dendritic spine density, specifically within dentate gyrus and CA3 regions rather than CA1 region. The findings suggest that voluntary exercise during development can enhance spatial memory in mice by increasing synapse numbers and improving synaptic transmission in hippocampal dentate gyrus and CA3 regions, but not in CA1 region. This study sheds light on the neural mechanisms underlying how early-life exercise improves cognitive function.
研究领域:
神经科学
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行为学
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DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2025
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IF 3.7
Ting Chen,Junke Jia,Chenyi Gao,Qi Zhong,Lijuan Tang,Xiaokai Sui,Shuang Li,Chang Chen,Zongze Zhang
Sleep plays a crucial role in restoring and repairing the body, consolidating memory, regulating emotions, maintaining metabolic and so on. Sleep deprivation is known to impair cognitive functions. In this study, we investigated the mechanisms underlying memory impairment induced by sleep deprivation through a combined metabolomic and transcriptomic analysis of hippocampus. Eight-week-old mice were selected as the study subjects and the sleep deprivation chamber was used to establish a sleep deprivation (SD) model. Novel object recognition tests (NOR), and Y-maze tests were used to assess the behavioral outcomes in mice. The hippocampus were extracted and studied using the untargeted metabolomics or transcriptomics high-throughput sequencing method. An integrative analysis was conducted to elucidate the metabolic and genetic changes. Behavioral tests showed that SD group exhibited memory impairment. Metabolomic analysis identified 84 differentially expressed metabolites (DEMs), including 12 under the positive ion mode and 72 under the negative ion mode. The analysis revealed that sleep deprivation caused abnormalities in several metabolic pathways, with particularly pronounced effects observed in glycerophospholipid metabolism, linoieic acid metabolism, alanine, aspartate, glutamate metabolism, taurine and hypotaurine metabolism, and purine metabolism. While transcriptomic analysis releaved 97 differentially expressed genes (DEGs) (51 were down-regulated and 46 were up-regulated DEGs). Integrative analysis of the metabolomic and transcriptomic identified profiles showed that sleep deprivation may regulate taurine and hypotaurine metabolism and sphingolipid metabolism, there by influencing memory. Our results prompt severe metabolic disturbances occur in the hippocampus with SD in mice, which can provide a basis for the mechanism research.
研究领域:
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
BIOMEDICAL CHROMATOGRAPHY
·
2022
·Vol. 36
·期 10
·e5435
·
IF 1.911
Jing Zhang,Jun-qing Yang,Ying Luo,Jian-sha Li,Tao Gong,Su-qiong Huang,Yan Xiong,Xin-hui Jiang
The study of brain diseases has long been of interest to researchers worldwide, and stroke is the third leading cause of death that threatens human health. At the same time, cerebral ischemia–reperfusion injury is closely associated with high rates of disability and mortality. The conditions of the 6-aminoquinolyl N -hydroxysccinimidyl carbamate method for the derivatization of amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice with cerebral ischemia–reperfusion injury were explored and optimized, such as the column temperature, concentration of derivatization reagents and mobile phase concentration. The mobile phase consisted of 20 m m sodium acetate solution (phosphoric acid to adjust pH 5.0) and 60% acetonitrile solution at a flow rate of 1 ml min −1 . The 23 analytes were separated and determined in a gradient elution procedure; the correlation coefficient r was >0.9990 in the range 0.1–8.0 μg ml −1 . The results showed that the content of relevant analytes was significantly changed in the cerebral ischemia–reperfusion injury model, and the method was suitable for the simultaneous determination of 23 amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice.
研究领域:
神经生物学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2021
·Vol. 23
·期 4
·1-1
·
IF 2.952
Guang Chen,Gang Yu,Zheng Yong,Hui Yan,Ruibin Su,Huijun Wang
Drug addiction is a chronic and recurrent disease associated with learning and memory. Shaped by drug use and cues from the environment, drug memory serves a key role in drug‑seeking behaviour. Methamphetamine (MA), a globally abused drug, causes cognitive impairment, and endoplasmic reticulum (ER) stress is one of the mechanisms via which this occurs. In the current study, it was hypothesized that ER stress may serve a role in the disturbance of drug memory. The present study demonstrated that 5 mg/kg MA inhibited conditioned place preference behaviour via ER stress, which caused a disruption in long‑term potentiation in the hippocampus. When mice were pre‑treated with the ER stress inhibitors 4‑phenyl butyric acid or tauroursodeoxycholic acid, drug‑evoked synaptic plasticity was induced. Western blotting results indicated that treatment with 5 mg/kg MA enhanced the expression of cyclin‑dependent kinase‑5 and decreased the expression of Ca2+/calmodulin‑dependent protein kinase II α via ER stress. Collectively, the present results suggested that a large dose of MA inhibited drug‑evoked synaptic plasticity and disrupted drug memory by inducing ER stress.
研究领域:
神经科学
·
药理学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Qishuo Wang,Yixuan Wu,Yunqing Wang,Rongchao Mei,Rui Zhao,Xiaoyan Wang,Lingxin Chen
Rapid and precise DNA barcode-based identification of biological species holds significant potential for pharmaceutical authentication and biomedical diagnostics. Herein, we present a polymerase chain reaction (PCR)–surface-enhanced Raman scattering (SERS) platform that integrates SERS tags for ultrasensitive and fast authentication of Hippocampus trimaculatus , a high-value traditional Chinese medicine (TCM). The SERS tags are composed of gold nanostars, near-infrared cyanine7 Raman reporters and carboxylated polystyrene shells, which achieve single-particle detection sensitivity under 780 nm irradiation. The tags also show excellent colloidal and SERS stability under physiologically relevant conditions (e.g., phosphate buffer saline, serum, 1 mM NaCl, and pH 1–12), with signal variations less than 5 %. The carboxylated polystyrene shells enable efficient DNA functionalization. Leveraging these advancements, the PCR-SERS assay detects genomic DNA (gDNA) at concentrations as low as 10 copies/μL within 20 thermal cycles, with remarkable specificity for Hippocampus trimaculatus over four common adulterant species. Notably, the method reduces amplification requirements to 5 thermal cycles (detection limit of 10 6 copies/μL) while completing the entire workflow in less than 30 min (conventional qPCR, 20–30 cycles, 1–2 h). Beyond TCM verification, this PCR-SERS platform holds broad applicability for rapid nucleic acid detection in fields ranging from environmental eDNA monitoring to point-of-care diagnostics.
研究领域:
生物技术
·
中药学
·
分子诊断
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2017
·Vol. 41
·期 5
·e12391
·
IF 1
Wei Liao,Yangfeng Liu,Guanghua Xia,Xuan Ri Shen,Zhouwei Duan,Jian Yang
In current study, three-spot seahorse ( Hippocampus trimaculatus ) skin collagen (SC) was extracted for the first time, and its physicochemical properties were characterized. Nile tilapia-skin collagen (TC) and pig-skin collagen (PC) were used to the references. The yields of SC and TC were 40.41 ± 1.23 and 52.6 ± 0.97% (dry weight), respectively. The SDS-PAGE and FTIR confirmed that SC, TC, and PC were preliminarily identified as type I collagen with triple helical structure. The denaturation temperatures of SC, TC, and PC were 35.12, 38.66, and 42.56°C, respectively. Gel-forming studies indicated SC exhibited higher capability than TC and PC under the effect of NaCl. After cross-linking by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), SC showed a significant increase in thermal stability and mechanical strength, and electron microscopic observation corroborated this phenomenon. Therefore, the isolated collagen from three-spot seahorse skin can be used in food packaging and biomaterials as alternatives to mammalian collagen. Practical applications In this study, we evaluated a new source of skin collagen from three-spot seahorse which has been large-scale artificially cultured in recent years. The finding of this study demonstrate that SC exhibited higher gel-forming capability under the effect of NaCl, which suggest that it may be used in photographic film, sausage casings, and food additive as alternatives to mammalian collagen. Furthermore, thermal stability and mechanical strength of SC gel have a significant increase after cross-linking by EDC, so it can be further used for biomaterials, such as food packaging, drug delivery, tissue engineering constructs, and wound dressing systems.
研究领域:
食品科学
·
生物材料学
·
海洋生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）