Neurosignals最新文献_第6页

Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression 抗抑郁药物对酸性鞘磷脂酶的抑制作用可抵消应激诱导的重性抑郁症患者p38激酶的激活

Neurosignals Pub Date : 2015-12-01 DOI: 10.1159/000442606

H. Grassmé, P. Jernigan, R. Hoehn, B. Wilker, Matthias Soddemann, M. Edwards, C. Müller, J. Kornhuber, E. Gulbins

{"title":"Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression","authors":"H. Grassmé, P. Jernigan, R. Hoehn, B. Wilker, Matthias Soddemann, M. Edwards, C. Müller, J. Kornhuber, E. Gulbins","doi":"10.1159/000442606","DOIUrl":"https://doi.org/10.1159/000442606","url":null,"abstract":"Background/Aims: Major depressive disorder is a common disease with serious morbidity, including increased risk of death from suicide. Major depressive disorder is treated with antidepressants. However, the molecular targets of antidepressants remained ill-defined and require further elucidation. Methods: Mice were treated with corticosterone to induce stress, amitriptyline and the p38-kinase (p38K) inhibitor SB239063 or a combination of these drugs. Phosphorylation of p38K in hippocampal neurons was determined by immunostaining with a phospho-specific antibody, neuronal proliferation using BrdU-labelling and behaviour employing a set of behavioural tests. Results: Corticosterone induced phosphorylation/activation of p38K in the hippocampus in vivo. Antidepressants reversed the effect of corticosterone on p38K activation in wildtype mice, but had no effect in acid sphingomyelinase-deficient animals. Corticosterone also reduced neurogenesis and triggered depression-like behavioural changes, effects that were prevented by pharmacological inhibition of p38K. Conclusion: Stress induces p38K phosphorylation/activation in the hippocampus and thereby reduces neurogenesis and induces depression-like symptoms, events that are prevented by antidepressants via inhibition of the acid sphingomyelinase/ceramide system.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"84 - 92"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Lithium- Sensitive Store-Operated Ca2+ Entry in the Regulation of FGF23 Release 锂敏感存储操作Ca2+进入调控FGF23释放

Neurosignals Pub Date : 2015-12-01 DOI: 10.1159/000442602

Bingbing Zhang, Jing Yan, Sebastian Schmidt, M. Salker, D. Alexander, M. Föller, F. Lang

{"title":"Lithium- Sensitive Store-Operated Ca2+ Entry in the Regulation of FGF23 Release","authors":"Bingbing Zhang, Jing Yan, Sebastian Schmidt, M. Salker, D. Alexander, M. Föller, F. Lang","doi":"10.1159/000442602","DOIUrl":"https://doi.org/10.1159/000442602","url":null,"abstract":"Background/Aims: Lithium, a widely used drug for the treatment of mood disorders, has previously been shown to stimulate the release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH)2D3 formation and mineral metabolism. The cellular mechanisms involved have remained elusive. Lithium has been shown to modify Ca2+ signaling. In a wide variety of cells, Ca2+ entry is accomplished by the pore-forming Ca2+ channel subunit Orai1 and its regulator STIM, which stimulates Orai following Ca2+ depletion of intracellular stores. Transcription factors promoting Orai1 expression include NF-κB. The present study thus explored whether the effect of lithium on FGF23 involves and requires Ca2+ entry. Methods: Experiments were performed in UMR106 osteoblastic cells and immortalized primary osteoblasts (IPO). FGF23 and Orai1 transcript levels were estimated from qRT-PCR, cytosolic Ca2+ concentration ([Ca2+]i) from Fura2 fluorescence and store-operated Ca2+ entry (SOCE) from an increase in [Ca2+]i following store depletion by inhibition of the sarcoendoplasmatic Ca2+ ATPase (SERCA) with thapsigargin (1 µM). Results: SOCE in UMR106 cells was enhanced by lithium treatment, an effect abrogated by Orai1 inhibitor 2-APB (50 µM). FGF23 transcript levels were increased by lithium and inhibited by Orai1 inhibitors 2-APB (50 µM) and YM58483 (100 nM) as well as NF-κB inhibitors wogonin (100 µM) and withaferin A (500 nM). Moreover, Orai1 transcript levels were up-regulated by lithium, an effect attenuated by wogonin and withaferin A. Conclusion: Lithium stimulates FGF23 release at least in part by NF-κB dependent up-regulation of Orai1 transcription and store operated Ca2+ entry.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"34 - 48"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells 嗜铬细胞瘤(PC12)细胞中Chorein敏感的多巴胺释放

Neurosignals Pub Date : 2015-12-01 DOI: 10.1159/000442599

Sabina Honisch, B. Fehrenbacher, Aleksandra A Lebedeva, I. Alesutan, T. Castor, Saad Alkahtani, S. Alarifi, M. Schaller, C. Stournaras, F. Lang

{"title":"Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells","authors":"Sabina Honisch, B. Fehrenbacher, Aleksandra A Lebedeva, I. Alesutan, T. Castor, Saad Alkahtani, S. Alarifi, M. Schaller, C. Stournaras, F. Lang","doi":"10.1159/000442599","DOIUrl":"https://doi.org/10.1159/000442599","url":null,"abstract":"Background: Chorein, a protein supporting activation of phosphoinositide 3 kinase (PI3K), participates in the regulation of actin polymerization and cell survival. A loss of function mutation of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) leads to chorea-acanthocytosis (ChAc), a neurodegenerative disorder with simultaneous erythrocyte akanthocytosis. In blood platelets chorein deficiency has been shown to compromise expression of vesicle-associated membrane protein 8 (VAMP8) and thus degranulation. The present study explored whether chorein is similarly involved in VAMP8 expression and dopamine release of pheochromocytoma (PC12) cells. Methods: Chorein was down-regulated by silencing in PC12 cells. Transmission electron microscopy was employed to quantify the number of vesicles, RT-PCR to determine transcript levels, Western blotting to quantify protein expression and ELISA to determine dopamine release. Results: Chorein silencing significantly reduced the number of vesicles, VAMP8 transcript levels and VAMP8 protein abundance. Increase of extracellular K+ from 5 mM to 40 mM resulted in marked stimulation of dopamine release, an effect significantly blunted by chorein silencing. Conclusions: Chorein deficiency down-regulates VAMP8 expression, vesicle numbers and dopamine release in pheochromocytoma cells.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"1 - 10"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

SPAK and OSR1 Sensitive Kir2.1 K+ Channels SPAK和OSR1敏感Kir2.1 K+通道

Neurosignals Pub Date : 2015-12-01 DOI: 10.1159/000442601

Myriam Fezai, Musaab Ahmed, Z. Hosseinzadeh, B. Elvira, F. Lang

{"title":"SPAK and OSR1 Sensitive Kir2.1 K+ Channels","authors":"Myriam Fezai, Musaab Ahmed, Z. Hosseinzadeh, B. Elvira, F. Lang","doi":"10.1159/000442601","DOIUrl":"https://doi.org/10.1159/000442601","url":null,"abstract":"Background/Aims: Kir2.1 (KCNJ2) channels are expressed in neurons, skeletal muscle and cardiac tissue and maintain the resting membrane potential. The activity of those channels is regulated by diverse signalling molecules. The present study explored whether Kir2.1 channels are sensitive to the transporter and channels regulating kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are in turn regulated by WNK (with-no-K[Lys]) kinases. Methods: cRNA encoding Kir2.1 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Inwardly rectifying K+ channel activity was quantified utilizing dual electrode voltage clamp and Kir2.1 channel protein abundance in the cell membrane was measured utilizing chemiluminescence of Kir2.1 containing an extracellular HA-tag epitope. Results: Kir2.1 activity was significantly enhanced by wild-type SPAK and T233ESPAK, but not by T233ASPAK and D212ASPAK, as well as by wild-type OSR1 and T185EOSR1, but not by T185AOSR1 and D164AOSR1. As shown for SPAK, the kinases enhanced Kir2.1 protein abundance in the cell membrane. The difference of current and conductance between oocytes expressing Kir2.1 together with SPAK or OSR1 and oocytes expressing Kir2.1 alone was dissipated following a 24 hours inhibition of channel insertion into the cell membrane by brefeldin A (5 µM). Conclusions: SPAK and OSR1 are both stimulators of Kir2.1 activity. They are presumably effective by enhancing channel insertion into the cell membrane.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"20 - 33"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology 新发精神病的脑弥散变化及状态依赖性精神病理的影响

Neurosignals Pub Date : 2015-12-01 DOI: 10.1159/000442605

A. Schmidt, C. Lenz, R. Smieskova, F. Harrisberger, A. Walter, A. Riecher-Rössler, A. Simon, U. Lang, P. McGuire, P. Fusar-Poli, S. Borgwardt

{"title":"Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology","authors":"A. Schmidt, C. Lenz, R. Smieskova, F. Harrisberger, A. Walter, A. Riecher-Rössler, A. Simon, U. Lang, P. McGuire, P. Fusar-Poli, S. Borgwardt","doi":"10.1159/000442605","DOIUrl":"https://doi.org/10.1159/000442605","url":null,"abstract":"Background/Aims: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). Methods: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. Results: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. Conclusion: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"71 - 83"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Targeting the Small- and Intermediate-Conductance Ca-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface. 靶向小电导和中电导钙活化钾通道:通道/钙调蛋白界面的药物结合口袋。

Neurosignals Pub Date : 2014-01-01 Epub Date: 2014-10-08 DOI: 10.1159/000367896

Meng Cui, Guangrong Qin, Kunqian Yu, M Scott Bowers, Miao Zhang

{"title":"Targeting the Small- and Intermediate-Conductance Ca-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface.","authors":"Meng Cui, Guangrong Qin, Kunqian Yu, M Scott Bowers, Miao Zhang","doi":"10.1159/000367896","DOIUrl":"https://doi.org/10.1159/000367896","url":null,"abstract":"The small- and intermediate-conductance Ca(2+)-activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca(2+) sensitivity of the SK/IK channels stems from a constitutively bound Ca(2+)-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca(2+) sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"22 2","pages":"65-78"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000367896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32733492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Hedgehog and Notch signaling in enteric nervous system development. 肠神经系统发育中的Hedgehog和Notch信号。

Neurosignals Pub Date : 2014-01-01 Epub Date: 2013-12-14 DOI: 10.1159/000356305

Jessica Ai-jia Liu, Elly Sau-Wai Ngan

引用次数: 28

Electrophysiological Features of Neurons in the Mesencephalic Trigeminal Nuclei. 中脑三叉神经核神经元的电生理特征。

Neurosignals Pub Date : 2014-01-01 Epub Date: 2015-01-09 DOI: 10.1159/000369822

Jun-Ling Xing, San-Jue Hu, Jing Yang

引用次数: 3

AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage. AxonQuant:一个微流体室培养耦合算法，允许轴突损伤的高通量定量。

Neurosignals Pub Date : 2014-01-01 Epub Date: 2014-02-28 DOI: 10.1159/000358092

Yang Li, Mengxue Yang, Zhuo Huang, Xiaoping Chen, Michael T Maloney, Li Zhu, Jianghong Liu, Yanmin Yang, Sidan Du, Xingyu Jiang, Jane Y Wu

{"title":"AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage.","authors":"Yang Li, Mengxue Yang, Zhuo Huang, Xiaoping Chen, Michael T Maloney, Li Zhu, Jianghong Liu, Yanmin Yang, Sidan Du, Xingyu Jiang, Jane Y Wu","doi":"10.1159/000358092","DOIUrl":"https://doi.org/10.1159/000358092","url":null,"abstract":"Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an 'axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":" ","pages":"14-29"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000358092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40287414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Regulator of G protein signaling transcript expression in human neural progenitor differentiation: R7 subfamily regulation by DNA methylation. G蛋白信号转录物在人神经祖细胞分化中的表达调控:R7亚家族通过DNA甲基化调控。

Neurosignals Pub Date : 2014-01-01 Epub Date: 2014-06-04 DOI: 10.1159/000362128

Katie Tuggle, Mourad W Ali, Hector Salazar, Shelley B Hooks

{"title":"Regulator of G protein signaling transcript expression in human neural progenitor differentiation: R7 subfamily regulation by DNA methylation.","authors":"Katie Tuggle, Mourad W Ali, Hector Salazar, Shelley B Hooks","doi":"10.1159/000362128","DOIUrl":"https://doi.org/10.1159/000362128","url":null,"abstract":"G protein-coupled receptors (GPCRs) and their ligands are critical regulators of neural progenitor differentiation, and GPCR signaling pathways are regulated by regulator of G protein signaling (RGS) proteins. RGS protein expression is dynamically regulated, and we have recently described the epigenetic regulation of RGS transcript expression. Given the potential of RGS proteins to regulate GPCR signaling and the established role of epigenetic regulation in progenitor differentiation, we explored the impact of epigenetic regulation of RGS transcripts during in vitro differentiation of human neural progenitors. Here, we demonstrate robust upregulation of the RGS transcripts RGS4, RGS5, RGS6, RGS7, and RGS11 during neuronal differentiation, while DNA methyltransferase (DNMT) and histone deacetylase enzyme expression is suppressed during differentiation. Transcripts encoding R7 subfamily RGS proteins and the R7-binding partners R7BP and R9AP showed the greatest upregulation. Further, we showed that direct pharmacological inhibition of DNMT activity enhances expression of RGS2, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9L, RGS10, and RGS14 as well as R7BP and R9AP transcripts in progenitors, consistent with regulation by DNMTs. Our results reveal marked upregulation of RGS expression during neuronal differentiation and suggest that decreased expression of DNMT enzymes during differentiation contributes to upregulation. © 2014 S. Karger AG, Basel","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"22 1","pages":"43-51"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000362128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32401318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12