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Effects of acute and chronic administration of MK-801 on c-fos protein expression in mice brain regions implicated in schizophrenia and antagonistic action of clozapine

Effects of acute and chronic administration of MK-801 on c-F...

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两岸三地药理学与临床药理学术会议

作者： ZUO Dai-ying~1 cAO Yue~2 ZHANG Lan~1 WANG Hai-feng~1 WU Ying-liang~1 (1. Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, china 2. Liaoning Institute for Drug control, Shenyang 110023, china)

Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-fos protein expression in different brain regions of mice and an- tagonistic action of *** Immunohistochemistry was used to detect the expression of c-fos *** MK-801(0.6mg·kg)acute administration produced a significant increase in the expres- sion of c-fos protein in the layersⅢ-Ⅳof posterior cingulate and retrosplenial(Pc/RS)cortex,which was consistent with the previous ***,we presented a new finding that MK-801(0.6 mg·kg) chronic administration for 8 days produced a significant increase of c-fos protein expression in the Pc/RS cortex,prefrontal cortex(PFc)and hypothalamus of *** that,c-fos protein expression in the Pc/ RS cortex of mice was most *** acute administration with chronic administration,we found that MK-801 chronic administration significantly increased the expression of c-fos protein in the Pc/ RS cortex,PFc and ***,pretreatment of mice with clozapine significantly decreased the expression of c-fos protein induced by MK-801 acute and chronic *** Marked expression of c-fos protein induced by MK-801 is associated with neurotransmitters’change noted in our previous studies,and c-fos protein,the marker of neuronal activation,might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.

关键词： c-fos protein clozapine MK-801 schizophrenia

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EXPRESSION AND SIGNIFIcANcE OF ONcOprotein p16 AND fos IN OSTEOSARcOMA

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chinese Journal of cancer Research 2001年第1期13卷 66-68页

作者：喻爱喜陈振光鲁德银余国荣 Department of Microsurgery Second Affiliated Hospital Hubei Medical University Wuhan Department of Tumor Pathology Hubei Medical University Wuhan

Objective: To investigate p16, c-fos protein expression and their relationships in osteosarcoma. Methods: Immunohistochemical technique (SABc) was used to detect p16 and c-fos protein expression in 41 cases of osteosarcoma. Results: The positive rates of p16 and c-fos protein expression were 51.2% and 82.9% respectively. Their expression was not correlated to pathological subtype, but correlated to clinic grade, and the latter was associated with tumor metastasis. There was a negative correlation between p16 and c-fos protein expression. conclusion: The alteration of p16 and c-fos protein expression may be related to the tumorigenesis and development of osteosarcoma, and c-fos proteins may take part in osteosarcoma metastasis. These data will offer useful helpness to determine the prognosis of osteosarcoma.

关键词： p16 protein c-fos protein Osteosarcoma Immunohistochemistry

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Expression of c-fos in gastric myenteric plexus and spinal cord of rats with cervical spondylosis

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World Journal of Gastroenterology 2005年第4期11卷 529-533页

作者： Pei-SongSong Kang-MeiKongx Kang-MeiKong chun-YanNiu Wei-LiQi Ling-FeiWu Xin-jiaWang WeiHan KengHuang Ze-Fengchen DepartmentofJointandSpine SecondAffiliatedHospitalShantouUniversityMedicalCollegeShantou515041GuangdongProvinceChina DepartmentofGastroenterology SecondAffiliatedHospitalShantouUniversityMedicalCollegeShantou515041GuangdongProvinceChina DepartmentofGastroenterology SecondHospitalofXi'anJiaotongUniversity.Xi'an710004.ShaanxiProvince.China

AIM: To determine the expression of c-fos in gastric myenteric plexus and spinal cord of rats with cervical spondylosis and its clinical significance. METHODS: A cervical spondylosis model was established in rats by destroying the stability of cervical posterior column,and the cord segments c4-6 and gastric antrum were collected 3, 4 and 5 mo after the operation. Rats with sham operation were used as controls. c-fos neuronal counter-staining was performed with an immunohistochemistry method. Every third sections from c4-6 segments were drawn. The 10 most labeled c-fos-immunoreactive (fos-IR) neurons were counted, and the average number was used for statistical analysis. The mean of fos-IR neurons in myenteric plexus was calculated after counting fos-IR neurons in 25 ganglia from each antral preparation, and expressed as a mean count per myenteric ***: There were a few c-fos-positive neurons in the cervical cord and antrum in the control group. There was an increased c-fos expression in model group 3, 4 and 5 mo after operation, whereas there was no significant increase in c-fos expression in the control group at 3, 4 and 5 *** importantly, there was a significant difference in c-fos expression between rats followed up for 3 mo and those for 5 mo in the model group (11.20±2.26 vs 27.68±4.36,P＜0.05, for the cervical cord; and 11.3±2.3 vs 29.3±4.6,P＜0.05, for the gastric antrum). There was no significant difference between rats followed up for 3 mo and those for 4 mo and between rats followed up for 4 mo and those for 5 mo in the model ***: c-fos expression in gastric myenteric plexus was dramatically associated with that in the spinal cord in rats with cervical spondylosis, suggesting that the gastrointestinal function may be affected by cervical spondylosis. If this hypothesis is confirmed by further studies, functional gastrointestinal diseases such as functional dyspepsia and irritable bowel syndrome could be explained by neurogastroen

关键词： Gastric myenteric plexus Gastric spinal cord c-fos protein cervical spondylosis

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Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula

Why depression and pain often coexist and mutually reinforce...

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中国神经科学学会第十二届全国学术会议

作者： Jicheng Li Yang Li Beilin Zhang Xiangfeng Shen Hua Zhao Department of Physiology College of Basic Medical Sciences Jilin University

The interrelation of depression and pain is increasingly coming under scrutiny. Although the lateral habenula（LHb） is widely implicated in the pathogenesis of depression and pain, its role in the interaction of depression and pain remains unknown. Thus, the aim of current study was to investigate the role of LHb in rat depression-pain comorbidity. Single extracellular firing recording and immunofluorescence methods were used to compare firing rates and c-fos expression of the LHb neurons in normal and model rats. Following subcutaneous injection of formalin into the hind paw to simulate natural pain, we assessed pain behavior in rats subjected to the chronic, unpredictable mild stress procedure（cUMS, a model of depression）. Pain sensitivity in the model rats was increased over that of controls. These rats showed a significant increase in the firing activity of LHb neurons compared with normal rats. Significantly, about 73% of neurons with high discharge frequency in LHb of model rats were pain-activated neurons（PANs）, and the firing rates of PANs were inhibited by intraperitoneal injection of a tricyclic antidepressant, clomipramine. Immunofluorescence showed that the percentage of c-fos positive cells in LHb was significantly increased in rats receiving cUMS alone, rats receiving pain stimulation alone, and rats receiving both cUMS and pain stimulation, but especially the last. The interaction effect was inhibited by injection of clomipramine. The LHb lesion can improve both depression-like behavior and pain sensitivity in depression model rats with pain. These suggest that hyperactivity of the LHb neurons contributes to depression-pain comorbidity in rats.

关键词： Depression Pain Lateral habenula Dorsal raphe nucleus c-fos protein comorbidity

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流动剪切力对培养人脐静脉内皮细胞原癌基因c-fos和c-myc蛋白表达的影响

流动剪切力对培养人脐静脉内皮细胞原癌基因c-fos和c-myc蛋白表达...

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作者：李彩霞北京工业大学

学位级别：硕士

内皮细胞位于血管最内层，持续不断得暴露于血液流动产生的血流应力的作用下。内皮细胞具有多种生理功能，其结构和功能的改变对血液流动性、血管张力及通透性调节方面都有影响，严重时引发病变。血液流动产生的剪切力（Fluid Shear Fo... 详细信息

内皮细胞位于血管最内层，持续不断得暴露于血液流动产生的血流应力的作用下。内皮细胞具有多种生理功能，其结构和功能的改变对血液流动性、血管张力及通透性调节方面都有影响，严重时引发病变。血液流动产生的剪切力（Fluid Shear Force或Shear Force）就是影响血管内皮细胞形态和功能的重要因素之一。原癌基因是在内皮细胞受刺激后短时间内通过一定的信号转导通道而诱导其表达的，近年来，原癌基因在国际上越来越引起关注。所以，为了探索剪切力对内皮细胞原癌基因表达的影响，我们以体外培养的人脐静脉内皮细胞为研究对象，借助平行板流动小室装置，利用免疫组织化学方法及计算机图象处理研究了内皮细胞原癌基因c-fos和c-myc蛋白在不同的剪切力作用下随时间的表达规律。这对于进一步探究内皮细胞通过何种信号传导途径将剪切力信号和刺激传入内皮细胞内并引起一系列的细胞应答和认识流动剪切力作用对血管内皮细胞功能、代谢等产生的影响以及对某些疾病的早期诊断等都有重要意义。我们的研究发现内皮细胞原癌基因c-fos蛋白表达在静态（无剪切力作用）时非常低，当施加剪切力后可诱导c-fos蛋白水平迅速增加。在我们实验中分别施加了4dynes/cm和10 dynes/cm两种剪应力。当剪应力大小为4 dynes/cm时，c-fos蛋白表达量随作用时间的延长而增加，到1.0小时达到高峰，与对照组相比有极显著差异（p＜0.001），随后下降，2.5小时时接近基础水平（对照组水平）。当剪应力大小是10 dynes/cm时，随时间的变化规律同剪应力为4 dynes/cm，但表达量较其大，说明c-fos蛋白表达具有剪切力作用时间和剪切力大小依赖性。同时，我们也发现c-myc蛋白在静态时表达也非常低，经剪切力作用后缓慢增加，c-myc蛋白水平明显较c-fos低（p＜0.05），而且剪应力为4 dynes/cm和10 dynes/cm两种情况对c-myc蛋白表达的影响无明显差异，其高峰在1.5小时，与对照组相比有显著差异（p＜0.05），随后下降在2.5小时时接近基础水平。说明c-myc蛋白表达具有剪切力作用时间的依赖性。实验同时发现剪切力过大或作用时间过长都可导致内皮细胞皱缩、损伤和脱落。以上的研究证实细胞在受剪切力作用后可通过一定的信号转导途径使c-fos蛋白和c-myc蛋白表达增加。而且，不同剪切力，即剪切力作用大小、持续时间不同，对其表达的调节也不同。因为原癌基因确实与人正常生理功能的发挥和一些疾病的发展有密切的联系。所以，我们的研究可能对于未来临床研究和一些疾病的诊断提供了有意义的线索。

关键词： fluid shear stress human umbilical vein endothelial cells c-fos protein c- myc protein

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脂多糖诱发急性牙髓炎致敏的三叉神经节功能蛋白质组学研究

脂多糖诱发急性牙髓炎致敏的三叉神经节功能蛋白质组学研究

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第七次全国颞下颌关节病学及（牙合）学研讨会暨《颞下颌关节紊乱病及口颌面疼痛的基础与临床进展》国家级继续教育学习班

作者：顾斌解放军总医院口腔科

目前,口腔颌面部急慢性疼痛的机制不明,而神经系统致敏的问题正是神经科学领域研究的难点和热点。在疼痛研究中,各种牙髓损伤动物模型具有很多优点,而急性牙髓炎是较为理性的病理性疼痛动物模型,对于研究牙髓和口颌面疼痛的机制具有重... 详细信息

目前,口腔颌面部急慢性疼痛的机制不明,而神经系统致敏的问题正是神经科学领域研究的难点和热点。在疼痛研究中,各种牙髓损伤动物模型具有很多优点,而急性牙髓炎是较为理性的病理性疼痛动物模型,对于研究牙髓和口颌面疼痛的机制具有重要价值。目的:本研究结合临床实际,采用开髓封LPS的方法,建立大鼠急性牙髓炎的病理性疼痛动物模型,应用蛋白质组学新技术,筛选与鉴定急性牙髓炎致敏时三叉神经节异常表达蛋白,寻找痛觉相关蛋白,探讨中枢致敏机制。材料与方法:雄性SD大鼠,设正常对照组和实验组。实验组动物左上第一磨牙开髓,封LPS,于24小时取三叉神经节组织,用蛋白质组学方法分析三叉神经节功能表达差异蛋白。结果:蛋白质组分析鉴定出48个差异点蛋白质斑点,其中21个表达量上调,27个下调,经质谱检测出10个点,分别为甲状腺素运载蛋白;内质网蛋白ERp29;低分子量神经丝蛋白;盘膜边缘蛋白;血清白蛋白前体;外周髓磷脂P0蛋白;组织蛋白酶B;丙酮酸脱氢酶E1;复制蛋白A和细胞骨架肌动蛋白。结论:开髓封LPS可以有效的造成急性牙髓炎动物模型,是较好的痛觉致敏模型;在鉴定的10种蛋白质中,包括了细胞结构蛋白、分子伴侣蛋白、生物合成相关蛋白、以及在应激反应和能量代谢等重要生命活动中起关键作用的酶,细胞骨架破坏、能量代谢改变、信号转导异常等共同参与了LPS急性牙髓致敏的形成;内质网蛋白ER29、神经丝蛋白及髓磷脂P0蛋白可能成为评价牙髓急性痛敏时程、疼痛程度及预测预后的生物指标,为进一步深入研究急性牙髓炎性致敏的分子机制提供重要的线索,对研究三叉神经节功能及口颌面部疼痛的诊断和治疗具有参考价值。

关键词： sensitization pain c-fos protein GFAP proteomics

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