Neurosignals最新文献

{"title":"Wnt / ß-Catenin Signaling Pathway Against Aβ Toxicity in PC12 Cells.","authors":"Yaping Zheng,&nbsp;Jin Wang,&nbsp;Deheng Li,&nbsp;Meixia Guo,&nbsp;Minghui Zhen,&nbsp;Quanzhong Chang","doi":"10.1159/000442610","DOIUrl":"https://doi.org/10.1159/000442610","url":null,"abstract":"<p><strong>Background/aims: </strong>Alzheimer's disease (AD) is characterized by accumulation of β-amyloid (Aβ), However, the mechanism of how Aβ affects neuronal cell death remains elusive. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bax) has been known to play a pivotal role in neuronal cell death. Of note, expression levels of these proteins are changed in the neurons in AD. To date no study has elusidated the relationship between Aβ and Bax.</p><p><strong>Methods: </strong>The present study explored the role of Wnt/β-catenin pathway in the neurotoxic effect of Aβ25-35. Flow cytometry was employed to determine the apoptosis, western blotting to assess the protein abundance of Bcl-2 and BAX, MTT assay to decipher the cells viability.</p><p><strong>Results: </strong>As a result, the addition of Wnt3a significantly prevented oligomeric Aβ-induced neuronal cell death and viability. Furthermore, treatment with Aβ25-35 increased Bax and Bcl-2 protein abundance and mRNA levels, an effect significantly blocked by Wnt3a (100 ng/ml) and GSK3β inhibitor TWS119 (10µM).</p><p><strong>Conclusion: </strong>These findings are first to demonstrate that Wnt/β-catenin signaling pathway regulates Aβ25-35-induced apoptosis.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"40-47"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34656083","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}

{"title":"Role of Janus-Kinases in Major Depressive Disorder.","authors":"Anne Gulbins,&nbsp;Heike Grassmé,&nbsp;Richard Hoehn,&nbsp;Marcus Kohnen,&nbsp;Michael J Edwards,&nbsp;Johannes Kornhuber,&nbsp;Erich Gulbins","doi":"10.1159/000442613","DOIUrl":"https://doi.org/10.1159/000442613","url":null,"abstract":"<p><strong>Background/aims: </strong>Major depressive disorder is a severe, common and often chronic disease with a significant mortality due to suicide. The pathogenesis of major depression is still unknown. It is assumed that a reduction of neurogenesis in the hippocampus plays an important role in the development of major depressive disorder. However, the mechanisms that control proliferation of neuronal stem cells in the hippocampus require definition. Here, we investigated the role of Janus-Kinase 3 (Jak-3) for stress-induced inhibition of neurogenesis and the induction of major depression symptoms in mice.</p><p><strong>Methods: </strong>Stress was induced by the application of glucocorticosterone. Brain sections were stained with phospho-specific antibodies and analysed by confocal microscopy to measure phosphorylation of Jak-3 specifically in the hippocampus. Jak-3 inhibitors and the antidepressant amitriptyline were applied to counteract stress. The effects of the inhibitors were determined by a set of behavioural tests and analysis of Jak-3 phosphorylation in brain sections. Acid sphingomyelinase-deficient mice were employed to test whether Jak3 is downstream of ceramide.</p><p><strong>Results: </strong>The data show that stress reduces neurogenesis, which is restored by simultaneous application of Jak-3 inhibitors. Inhibition of neurogenesis correlated with an anxious-depressive behaviour that was also normalized upon application of a Jak-3-inhibitor. Confocal microscopy data revealed that stress triggers a phosphorylation and thereby activation of Jak-3 in the hippocampus. Amitriptyline, a commonly used antidepressant that blocks the acid sphingomyelinase, or acid sphingomyelinase-deficiency reduced stress-induced phosphorylation of Jak-3.</p><p><strong>Conclusion: </strong>Our data show that Jak-3 is activated by stress at least partially via the acid sphingomyelinase and is involved in the mediation of stress-induced major depression.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"71-80"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34727663","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}

{"title":"Curcumin Protects against Monosodium Glutamate Neurotoxicity and Decreasing NMDA2B and mGluR5 Expression in Rat Hippocampus.","authors":"Rania M Khalil,&nbsp;Naglaa F Khedr","doi":"10.1159/000442614","DOIUrl":"https://doi.org/10.1159/000442614","url":null,"abstract":"<p><strong>Background: </strong>Monosodium glutamate (MSG) is a flavor enhancer used in food industries. MSG is well documented to induce neurotoxicity. Curcumin (CUR) reportedly possesses beneficial effects against various neurotoxic insults. Hence, this present study has been designed to evaluate the neuroprotective effect of curcumin on MSG-induced neurotoxicity in rats.</p><p><strong>Methods: </strong>Thirty-two male Wister rats were divided into four groups (n=8): Control group, MSG group, CUR group and MSG + CUR group. CUR (Curcumin 150 mg/kg, orally) was given day after day for four weeks along with MSG (4 mg/kg, orally). After 4 weeks, rats were sacrificed and brain hippocampus was isolated immediately on ice. Inflammatory marker TNFα and acetylcholinesterase (AChE) activity (marker for cholinergic function) were estimated. Gene expressions of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor 2B (NMDA2B) along with glutamate concentration were assessed.</p><p><strong>Results: </strong>Treatment with CUR significantly attenuated AChE activity and TNFα in MSG-treated animals. The anti-inflammatory properties of CUR may be responsible for this observed neuroprotective action. A possible role of CUR to attenuate both glutamate level and gene expression of NMDA2B and mGLUR5 in brain hippocampus was established when compared to MSG group.</p><p><strong>Conclusion: </strong>We concluded that CUR as flavor enhancer protects against MSG-induced neurotoxicity in rats.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"81-87"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34373062","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}

{"title":"Nogo-p4 Suppresses TrkA Signaling Induced by Low Concentrations of Nerve Growth Factor Through NgR1 in Differentiated PC12 Cells.","authors":"You-Ming Fan,&nbsp;Qing-Yuan Huang,&nbsp;Yin-Ai Wu,&nbsp;Alan R Harvey,&nbsp;Qi Cui,&nbsp;Yu-Qi Gao","doi":"10.1159/000442609","DOIUrl":"https://doi.org/10.1159/000442609","url":null,"abstract":"<p><strong>Background: </strong>Regeneration of injured axons in adult mammalian central nervous system (CNS) is not spontaneous. Nogo is a major inhibitory molecule contributing to axon regeneration failure. The molecular mechanisms of Nogo inhibition of axon regeneration are not completely understood. To further investigate the underlying mechanisms, we studied the effects of Nogo-p4, a 25-amino acid core inhibitory fragment of Nogo, on nerve growth factor (NGF)-induced TrkA signaling.</p><p><strong>Methods: </strong>NGF-differentiated PC12 cells were used as cell models. The effects of Nogo-p4 on two key components of TrkA signaling, phosphorylated Erk1/2 and Akt, were analyzed by western blot. Co-immunoprecipitation experiments were performed to detect the formation of NgR1/p75 complexes. Neurite growth was quantified by measuring the neurite length.</p><p><strong>Results: </strong>Nogo-p4 did not significantly affect TrkA signaling induced by 100 ng/ml NGF, but signaling was suppressed when an NGF concentration of 5 ng/ml was used. Further investigation demonstrated that Nogo-p4 affected TrkA signaling in an NGF concentration-dependent manner. Nogo-p4 suppression of TrkA signaling was strong at low (1 and 5 ng/ml), moderate at intermediate (25 ng/ml), but absent at high (50 and 100 ng/ml) NGF concentrations. NEP1-40 attenuated, and NgR1 overexpression enhanced, Nogo-p4 suppression of TrkA signaling induced by low concentrations of NGF. High but not low concentrations of NGF reduced the formation of NgR1/p75 complexes triggered by Nogo-p4. Nogo-p4 strongly inhibited neurite growth induced by low rather than high concentrations of NGF.</p><p><strong>Conclusion: </strong>Nogo-p4 binding with NgR1 suppresses TrkA signaling induced by low concentrations of NGF in differentiated PC12 cells. Suppression of NGF-induced TrkA signaling may be another mechanism by which Nogo inhibits neurite growth.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"25-39"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34576057","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}

{"title":"Gut Taste Stimulants Alter Brain Activity in Areas Related to Working Memory: a Pilot Study.","authors":"Anne Christin Meyer-Gerspach,&nbsp;Claudia Suenderhauf,&nbsp;Lukas Bereiter,&nbsp;Davide Zanchi,&nbsp;Christoph Beglinger,&nbsp;Stefan Borgwardt,&nbsp;Bettina K Wölnerhanssen","doi":"10.1159/000442612","DOIUrl":"https://doi.org/10.1159/000442612","url":null,"abstract":"<p><strong>Background/aims: </strong>Taste perception is one of the most important primary oral reinforcers, driving nutrient and energy intake as well as toxin avoidance. Taste receptors in the gastrointestinal tract might as well impact appetitive or aversive behavior and thus influence learning tasks and a close relation of neural taste processing and working memory networks seems plausible.</p><p><strong>Methods: </strong>In the present pilot study, we determined the effects of five taste qualities \"bitter\" (quinine), \"sweet\" (glucose), \"sour\" (citric acid), \"salty\" (NaCl) and \"umami\" (monosodium glutamate, MSG) on working memory processing using functional MRI and their effect on plasma insulin and glucose levels. On six separate occasions, subjects received one of the following test substances dissolved in 200 mL tap water via a nasogastric tube (to circumvent the oral cavity): 1) 2g citric acid corresponding to 52 mM, 2) 2g NaCl; 171 mM, 3) 0.017g quinine; 0.26 mM, 4) 1g monosodium glutamate; 30 mM, 5) 25g glucose; 694 mM and 6) 200 mL tap water (placebo).</p><p><strong>Results: </strong>The taste qualities \"bitter\" and \"umami\" significantly altered brain activation patterns in the primary gustatory cortex as well as in subcortical structures, previously reported to be involved in emotional learning and memory. In contrast, glucose did not reveal any statistically significant brain activation difference. Working memory performance was not different over the six treatments. Plasma insulin and glucose levels were not affected by the different taste substances (MSG, quinine, NaCl and citric acid).</p><p><strong>Conclusions: </strong>in this pilot trial, we demonstrate that acute intragastric administration of different taste substances does not affect working memory performance in humans. However, \"umami\" and \"bitter\" have effects on brain areas involved in neural working memory, overpowering the effects of \"sweet\", \"salty\" and \"sour\" reception.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"59-70"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34705907","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}

{"title":"Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System.","authors":"Richard Hoehn,&nbsp;Marlene Monse,&nbsp;Ella Pohl,&nbsp;Sina Wranik,&nbsp;Barbara Wilker,&nbsp;Simone Keitsch,&nbsp;Matthias Soddemann,&nbsp;Johannes Kornhuber,&nbsp;Marcus Kohnen,&nbsp;Michael J Edwards,&nbsp;Heike Grassmé,&nbsp;Erich Gulbins","doi":"10.1159/000442611","DOIUrl":"https://doi.org/10.1159/000442611","url":null,"abstract":"Background: Melatonin has been shown to have antidepressive effects. We tested whether melatonin inhibits the acid sphingomyelinase/ceramide system and mediates its antidepressive effects via inhibition of the acid sphingomyelinase and a reduction of ceramide in the hippocampus. Antidepressants such as amitriptyline and fluoxetine were previously shown to inhibit the acid sphingomyelinase/ceramide system, which mediates neurogenesis and behavioral changes induced by these drugs. Methods: The effect of melatonin on the activity of the acid sphingomyelinase prior to and after treatment with melatonin was determined in cultured neurons and in vivo in the hippocampus of mice by measuring the consumption of [14C] sphingomyelin. Ceramide was measured by DAG kinase assay and fluorescence microscopy of the hippocampus and of cultured neurons. Neurogenesis in the hippocampus was analyzed by in vivo labeling with bromodeoxyuridine. Behavior was assessed in standardized tests. Results: Melatonin treatment inhibited acid sphingomyelinase in vitro in cultured pheochromocytoma cells and in vivo in the hippocampus, which resulted in a reduction of ceramide in vitro and in vivo. The inhibition of the acid sphingomyelinase/ceramide system translated into increased neurogenesis in glucocorticosterone-stressed mice after treatment with melatonin, an effect that is abrogated in acid sphingomyelinase-deficient mice. Likewise, melatonin improved the depressive behavior of stressed mice, a therapeutic effect that was again absent in acid sphingomyelinase-deficient animals. Conclusion: These data indicate that the antidepressive effects of melatonin as well as the induction of neurogenesis triggered by this drug are mediated by an inhibition of the acid sphingomyelinase/ceramide system. This is the first study to identify melatonin as an inhibitor of the acid sphingomyelinase.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"48-58"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34719022","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}

{"title":"Leptin-Sensitive JAK2 Activation in the Regulation of Tau Phosphorylation in PC12 Cells.","authors":"Meixia Guo,&nbsp;Dongliang Li,&nbsp;Huijun Shen,&nbsp;Baijie Jin,&nbsp;Yankai Ren,&nbsp;Manli Li,&nbsp;Ying Xing","doi":"10.1159/000442615","DOIUrl":"https://doi.org/10.1159/000442615","url":null,"abstract":"<p><strong>Background/aims: </strong>Alzheimer's disease (AD) is characterized by two major hallmarks: the deposition and accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in intracellular neurofibrillary tangles. Sets of evidence show that leptin reduces Aβ production and tau phosphorylation. Herein, we investigated the signaling pathways activated by leptin, to extensively understand its mechanism.</p><p><strong>Methods: </strong>Western blotting was employed to assess the protein abundance of p-tau and BAX, MTT assay to decipher the cells viability.</p><p><strong>Results: </strong>Leptin decreased tau phosphorylation, an effect was dependent on the activation of JAK2.</p><p><strong>Conclusion: </strong>The data suggest that JAK2 is involved in AD-related pathways.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"88-94"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34727047","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}

{"title":"Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3","authors":"Myriam Fezai, J. Warsi, F. Lang","doi":"10.1159/000442600","DOIUrl":"https://doi.org/10.1159/000442600","url":null,"abstract":"Background: The creatine transporter CreaT (SLC6A8), a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. Methods: CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active A568VJAK3 and inactive K851AJAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Results: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or A568VJAK3, but not co-expression of K851AJAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 µM). Conclusion: JAK3 is a powerful negative regulator of the creatine transporter CreaT.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"45 1","pages":"11 - 19"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982704","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}

{"title":"Sphingolipids in Major Depression","authors":"P. Jernigan, R. Hoehn, H. Grassmé, M. Edwards, C. Müller, J. Kornhuber, E. Gulbins","doi":"10.1159/000442603","DOIUrl":"https://doi.org/10.1159/000442603","url":null,"abstract":"Major depression is one of the most common and severe diseases affecting the world's population. However, the pathogenesis of the disease remains inadequately defined. Previously, a lack of monoaminergic neurotransmitters was the focus of pathophysiological concepts; however, recent concepts focus on a alteration of neurogenesis in the hippocampus. This concept suggests that neurogenesis is decreased in major depression with a rarefication of neuronal networks and a lack of new, immature neurons in the hippocampus, events that may result in the clinical symptoms of major depression. However, molecular targets involved in the pathogenesis of major depression and, in particular, a reduction of neurogenesis, are largely unknown. We have recently discovered that an inhibition of the acid sphingomyelinase/ceramide system mediates the effects of tri- and tetracyclic antidepressants. Moreover, an accumulation of ceramide in the hippocampus results in depression-like symptoms. This suggests the acid sphingomyelinase/ceramide system is very important in the pathogenesis of major depression.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"49 - 58"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982749","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}

{"title":"Up-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by ß-Klotho","authors":"J. Warsi, Abeer Abousaab, F. Lang","doi":"10.1159/000442604","DOIUrl":"https://doi.org/10.1159/000442604","url":null,"abstract":"Background/Aims: Klotho, a transmembrane protein expressed in chorioid plexus of the brain, kidney, and several other tissues, is required for inhibition of 1,25(OH)2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. At least in part by exerting β-glucuronidase activity, soluble klotho regulates several ion channels and carriers. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The present study explored the effect of Klotho protein on the excitatory glutamate transporters EAAT1 (SLC1A3) and EAAT2 (SLC1A2), Na+ coupled carriers clearing excitatory amino acids from the synaptic cleft and thus participating in the regulation of neuronal excitability. Methods: cRNA encoding EAAT1 or EAAT2 was injected into Xenopus laevis oocytes and glutamate (2 mM)-induced inward current (IGlu) taken as measure of glutamate transport. Measurements were made without or with prior 24 h treatment with soluble ß-Klotho protein (30 ng/ml) in the absence and presence of β-glucuronidase inhibitor D-saccharic acid 1,4-lactone monohydrate (DSAL,10 µM). Results: IGlu was observed in EAAT1 and in EAAT2 expressing oocytes but not in water injected oocytes. In both, EAAT1 and EAAT2 expressing oocytes IGlu was significantly increased by treatment with soluble ß-Klotho protein, an effect reversed by DSAL. Treatment with ß-klotho protein increased significantly the maximal transport rate without significantly modifying the affinity of the carriers. Conclusion: ß-Klotho up-regulates the excitatory glutamate transporters EAAT1 and EAAT2 and thus participates in the regulation of neuronal excitation.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"23 1","pages":"59 - 70"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982757","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}