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A novel large animal model of recurrent migraine established by repeated administration of inflammatory soup into the dura mater of the rhesus monkey

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Neural Regeneration Research 2019年第1期14卷 100-106页

作者： Ning chen Wei Su Shu-Hui cui Jian Guo Jia-chuan Duan Hong-Xia Li Li He Department of Neurology West China Hospital Sichuan University Department of Science & Technology West China Hospital Sichuan University National chengdu center for Safety Evaluation of Traditional chinese Medicine West China Hospital Sichuan University

Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. However, most of these models have been established on lower animals, such as rodents, and involve only a single administration of a noxious stimulus. In this study, an inflammatory soup(10 μL), consisting of prostaglandin E2(0.2 mM), serotonin(2 mM), bradykinin(2 mM) and histamine(2 mM), was injected into the dura mater of conscious rhesus monkeys through an indwelling catheter. The infusion started on day 8 and was repeated every 3 days, for a total of six administrations, to induce neurogenic inflammation. We performed behavioral assessments and measured the expression of the oncogene c-fos, neuronal nitric oxide synthase(nNOS) and calcitonin gene related peptide(cGRP) in the trigeminal system and in multiple brain regions involved in pain processing by immunohistochemical staining. compared with monkeys in the control group, three of the four animals in the inflammatory soup group displayed decreased motor behaviors, and two showed increased ipsilateral nose and mouth secretions during the stimulus period. Higher expression levels of c-fos, nNOS and cGRP were found in various brain areas of experimental animals compared with controls, including the trigeminal nucleus caudalis, thalamus, hypothalamus, midbrain, pons and other areas involved in pain perception. These results suggest that repeated inflammatory soup stimulation of the dura activates the trigeminovascular system and produces migraine-like pathological changes and abnormal behaviors in conscious rhesus monkeys.

关键词：动物模型周期性恒河猴偏头痛母亲 c-fos 管理反常行为

学习记忆通路抑制剂T-5224和KN-62对翘嘴鳜c-fos及味觉受体t1r1表达的影响

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水生生物学报 2022年第6期46卷 880-887页

作者：肖倩倩梁旭方庄武元蔡文静华中农业大学水产学院华中农业大学鳜鱼研究中心武汉430070 长江经济带大宗水生生物产业绿色发展教育部工程研究中心武汉430070

为探究翘嘴鳜(Siniperca chuatsi)中原癌基因c-fos (proto-oncogene c-fos)对摄食相关的味觉受体t1r1(taste receptor type 1 member 1, t1r1)的调控作用,研究采用学习记忆通路相关抑制剂T-5224、KN-62处理鳜脑细胞,通过不同浓度抑制剂处理发现T-5224对c-fos的起负调控作用而KN-62对c-fos起正调控作用,同时筛选出适合的处理时间及浓度。30μmol/L T-5224处理24h,鳜脑中c-fos及t1r1的mRNA表达显著降低(Pc-fos及t1r1的mRNA表达却极显著升高(P0.05)。以上结果说明,翘嘴鳜脑细胞味觉受体t1r1转录水平变化,可能是通过学习记忆因子cfos基因调控,而c-fos可能通过其他途径调控t1r1的转录,但不是DNA甲基化。同时为翘嘴鳜驯化后摄食偏好变化提供理论依据。

关键词：学习记忆通路抑制剂 c-fos t1r1 DNA甲基化翘嘴鳜

Paraventricular Nucleus P2X7 Receptors Aggravate Acute Myocardial Infarction Injury via ROS-Induced Vasopressin-V1b Activation in Rats

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Neuroscience Bulletin 2021年第5期37卷 641-656页

作者： Wenjing cheng Yinggang Sun Qin Wu Kokwin Ooi Yi Feng chunmei Xia Danian Zhu Department of Physiology and Pathophysiology School of Basic Medical SciencesFudan UniversityShanghai 200032China Department of cardiovascular Diseases Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Medical Technology Jiangsu Vocational College of MedicineYancheng 224005China Department of Integrative Medicine and Neurobiology School of Basic Medical SciencesFudan UniversityShanghai 200032China

The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus(PVN) of the hypothalamus of rats with acute myocardial ischemia(AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG(brilliant blue G, a P2X7R antagonist), nelivaptan(a vasopressin V1b receptor antagonist), or diphenyleneiodonium(DPI) [an nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species(ROS) and NADPH oxidase 2(NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes.Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine(AE) levels in AMI rats. collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.

关键词： PVN P2X7 receptor Vasopressin Reactive oxygen species c-fos Myocardial ischemia

Illuminating the Activated Brain: Emerging Activity-Dependent Tools to capture and control Functional Neural circuits

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Neuroscience Bulletin 2019年第3期35卷 369-377页

作者： Qiye He Jihua Wang Hailan Hu center for Neuroscience and Department of Psychiatry of First Affiliated HospitalNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of MedicineHangzhou 310058China Interdisciplinary Institute of Neuroscience and Technology Qiushi Academy for Advanced StudiesZhejiang UniversityHangzhou 310012China

Immediate-early genes(IEGs) have long been used to visualize neural activations induced by sensory and behavioral stimuli. Recent advances in imaging techniques have made it possible to use endogenous IEG signals to visualize and discriminate neural ensembles activated by multiple stimuli, and to map whole-brain-scale neural activation at single-neuron resolution. In addition, a collection of IEG-dependent molecular tools has been developed that can be used to complement the labeling of endogenous IEG genes and, especially, to manipulate activated neural ensembles in order to reveal the circuits and mechanisms underlying different behaviors. Here, we review these techniques and tools in terms of their utility in studying functional neural circuits. In addition, we provide an experimental strategy to measure the signal-to-noise ratio of IEG-dependent molecular tools, for evaluating their suitability for investigating relevant circuits and behaviors.

关键词： Immediate-early gene Emotion Activity-dependent tools Neural ensembles c-fos Arc

Expression and significance of MMP-7,c-Jun and c-fos in rats skin photoaging

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Asian Pacific Journal of Tropical Medicine 2013年第10期6卷 768-770页

作者： Long-Quan Shi cai-Lian Ruan Department of Dermatology Affiliated Hospital of Yan'an University

Objective:To investigate the expression and significance of the MMP-7,c-Jun and c-fos in rat photoaging skin.Methods:A total of 45 SD rats were randomly divided into control group,model group,natural recovery group,physiological saline injection group and dermal pluripotent stem cells transplantation(DMScs group),model group,natural recovery group,physiological saline injection group.DMScs were treated with UV lamp irradiation to establish light aging skin model.Rats were then sacrificed after model prepared,no treatment was processed in the natural recovery group.Saline injections was adopted in saline group,DEScs group was treated with DEScs transplantation.Rats were sacrificed after 4 weeks.The expression of MMP-7,c-Jun and c-Kos were detected using the immunohistocheniical metluxl.Results:In model group,MMP 7positive expression was higher than that in the other 4 groups,but without statistically difference(P>0.05);c-Jun,c-fos expression were higher than that in the control group and DEScs group(Pcant difference comparing natural recovery group with physiological saline injection group(P>0.05).conclusions:MMP-7,c-Jun and c-fos can be used as diagnosis indicators in the early stage of light aging,and they jointly participate in its development.DMScs transplants is effective in treating light aging skin.

关键词： MMP-7 c-Jun c-fos Aging skin Expression

山羊转录因子c-fos克隆、鉴定及功能分析

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生物工程学报 2023年第4期39卷 1684-1695页

作者：胡婷婷王永陈定双龚成思李艳艳熊燕王建梅李志雄林亚秋西南民族大学畜牧兽医学院四川成都610041 西南民族大学青藏高原动物遗传资源保护与利用教育部/四川省重点实验室四川成都610041

转录因子c-fos在细胞增殖、分化和肿瘤形成中发挥着重要作用。本研究旨在获得山羊c-fos基因序列并阐明其生物学性质,进一步利用过表达手段揭示c-fos在山羊皮下脂肪细胞分化过程中的调控作用。本试验以简州大耳羊为研究对象,用逆转录PcR(... 详细信息

转录因子c-fos在细胞增殖、分化和肿瘤形成中发挥着重要作用。本研究旨在获得山羊c-fos基因序列并阐明其生物学性质,进一步利用过表达手段揭示c-fos在山羊皮下脂肪细胞分化过程中的调控作用。本试验以简州大耳羊为研究对象,用逆转录PcR(reverse transcription-polymerase chain reaction,RT-PcR)技术克隆获得c-fos基因序列并分析其生物学性质;用实时荧光定量PcR(quantitative PcR,qPcR)技术检测c-fos基因在山羊心、肝、脾、肺、肾、皮下脂肪和背最长肌7个组织以及皮下脂肪细胞诱导分化的0‒120 h的表达情况;用基因重组方法构建山羊pEGFP-c-fos过表达载体并转染至皮下前体脂肪细胞诱导分化后,用油红O和Bodipy染色从形态学上观察其对脂滴积聚的影响,用qPcR技术在mRNA水平上检测过表达c-fos对成脂分化标志基因的影响。结果表明,克隆的山羊c-fos基因长1477 bp[编码区(coding sequence,cDS)1143 bp],编码380个氨基酸,亚细胞定位预测该基因主要分布于细胞核中;表达蛋白具有一个碱性亮氨酸拉链结构;c-fos基因在山羊皮下脂肪组织相对表达水平较高(Pc-fos可抑制山羊皮下脂肪细胞的脂滴形成,并极显著降低成脂标志基因AP2和c/EBPβ的相对表达水平(Pc-fos是山羊皮下脂肪细胞分化的负调控因子,通过调控AP2和c/EBPβ基因的表达来发挥作用。

关键词：转录因子 c-fos 山羊皮下脂肪细胞分化

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

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Asian Pacific Journal of Tropical Medicine 2014年第10期7卷 761-764页

作者： Yan Zheng Guo-Rong Wang Jin-Jing Jia Su-ju Luo Hao Wang Sheng-Xiang Xiao Department of Dermatology the Second Affiliated Hospital of Xi'an Jiaotong University

Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(cScc).Methods:Using retrospective analysis.73 cases of cScc were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of cScc.The difference was statistically significant(X^2=7.26.P=0.001c-fos protein was positively related to differentiation of cScc.which was statistically significant(X^2=7.47,P=0.0012conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of cScc differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.

关键词： Oncogene protein c-fos Oncogene protein c-myc Squamous cell carcinoma Dermatoma

Effect of Transcranial Magnetic Stimulation on the Expression of c-fos and Brain-derived Neurotrophic Factor of the cerebral cortex in Rats with cerebral Infarct

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第4期27卷 415-418页

作者：张小乔梅元武刘传玉俞善纯 Department of Neurology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

The effect of transcranial magnetic stimulation （TMS） on the neurological functional recovery and expression of c-fos and brain-derived neurotrophic factor （BDNF） of the cerebral cortex in rats with cerebral infarction was investigated. cerebral infarction models were established by using left middle cerebral artery occlusion （McAO） and were randomly divided into a model group （n=40） and a TMS group （n=40）. TMS treatment （2 times per day, 30 pulses per time） with a frequency of 0.5 Hz and magnetic field intensity of 1.33 Tesla was carried out in TMS group after McAO. Modified neurological severity score （NSS） were recorded before and 1, 7, 14, 21, and 28 day（s） after McAO. The expression of c-fos and BDNF was immunohistochemically detected 1, 7, 14, 21, and 28 day（s） after infarction respectively. Our results showed that a significant recovery of NSS （P〈0.05） was found in animals treated by TMS on day 7, 14, 21, and 28 as compared with the animals in the model group. The positive expression of c-fos and BDNF was detected in the cortex surrounding the infarction areas, while the expression of c-fos and BDNF increased significantly in TMS treatment group in comparison with those in model group 7, 14, 21, and 28 days （P〈0.05） and 7 14, 21 days （P〈0.01） after infarction, respectively. It is concluded that TMS has therapeutic effect on cerebral infarction and this may have something to do with TMS＇s ability to promote the expression of c-fos and BDNF of the cerebral cortex in rats with cerebral infarction.

关键词： transcranial magnetic stimulation cerebral infarction neurological function c-fos brain-derived neurotrophic factor

c-fos expression within the L_5 spinal cord dorsal horn after spinal nerve ligation in rats Is intraplantar administration of glutamate different from intrathecal administration?

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Neural Regeneration Research 2010年第6期5卷 450-455页

作者： Youhong Jin Hongshui Zhu Zhihua Li Dongfang Li Jianhua Hu Motohide TakemuraO Norifumi YoneharaO Department of Anatomy Affiliated Stomatological Hospital of Nanchang University Nanchang 330006 Jiangxi ProvinceChina Department of Oral Anatomy and Neurobiology Osaka University Graduate School of Dentistry Suita 565-0871 Japan Divisions of Pharmacology Ohu University School of Pharmaceutical Science Koriyama Fukushima 963-8611 Japan

BAcKGROUND： Injection of glutamate （Glu） in normal animals can cause neuronal c-fos expression; however, whether Glu can induce spinal neuronal c-fos expression in pain models is unclear. OBJEcTIVE： To examine the effects of intraplantar and intrathecal injection of Glu on c-fos expression in the L5 spinal cord dorsal horn Ⅰ/Ⅱ and Ⅲ/Ⅳ layers after spinal nerve ligation, and to study the effects of the N-methyI-D-aspartic acid （NMDA） receptor antagonist, D-2-amino-5-phosphonopentanoate （D-AP5）, and a selective group I mGluR antagonist, 7-hydroyiminocyclo propan[a]chromen-lacarboxylic acid ethyl ester （cpccoEt）. DESIGN, TIME AND SETTING： A randomized, controlled animal study was performed at the Department of Pharmacology, Oral Anatomy, and Neurobiology, Osaka University Graduate School of Dentistry, from December 2005 to December 2006. MATERIALS： Glu （5 μmol）, D-AP5 （50 nmot） and cpccoEt （250 nmol） were provided by Wako Pure chemical Industries, Osaka, Japan, and diluted in saline （50 μL）. The pH of all solutions was adjusted to 7.4. METHODS： Twelve rats were randomly divided into sham operation （n = 6） and spinal nerve ligation （SNL; n = 6） groups for behavioral assessments of neuropathic pain after ligation surgery of the left L5-6 nerve segment. Another 60 rats were randomly divided into sham operation, SNL, saline-intraplantar, saline-intrathecal, Glu-intraplantar, Glu-intrathecal, D-AP5-intrathecal, Glu-D-AP5-intrathecal, cpccoEt-intrathecal, and Glu-cpccoEt-intrathecal groups, with 6 rats in each group. All groups except sham operation group received a similar SNL. On day 14, rats received a 50-μL injection of saline, Glu, D-AP5, and/or cpccoEt into the left intraplantar or intrathecal L5-4 segments. MAIN OUTcOME MEASURES： The number of c-fos positive neurons in both Ⅰ/Ⅱ and Ⅲ/Ⅳ spinal layers at L6 was observed using immunohistochemistry 2 hours after administration. RESULTS：（1） SNL increased the level of c-fos expression in two sides of the spinal cord, particularly on Ⅲ/Ⅳ spinal layers of the ligated side

关键词： spinal cord nerve ligation glutamate c-fos metabotropic glutamate receptors intrathecal administration intraplantar administration