Neurosignals最新文献

{"title":"Endomorphins: Promising Endogenous Opioid Peptides for the Development of Novel Analgesics.","authors":"Zheng-Hui Gu,&nbsp;Bo Wang,&nbsp;Zhen-Zhen Kou,&nbsp;Yang Bai,&nbsp;Tao Chen,&nbsp;Yu-Lin Dong,&nbsp;Hui Li,&nbsp;Yun-Qing Li","doi":"10.1159/000484909","DOIUrl":"https://doi.org/10.1159/000484909","url":null,"abstract":"<p><p>Endomorphin-1 (EM1) and endomorphin-2 (EM2) are two endogenous ligands that belong to the opioid peptide family and have the highest affinity and selectivity for the µ-opioid receptor (MOR). The neuroanatomical distribution, ultrastructural features and neural circuitry of EM-containing neuronal structures have been morphologically demonstrated. In addition, the modulation effects of the EMs in different areas reflect their potential endogenous roles in many major physiological processes, including their remarkable roles in the transmission and modulation of noxious information. The distinguished antinociceptive property of the EMs in acute and chronic pain, including neuropathic pain, cancer pain and inflammatory pain, has been revealed and investigated for therapeutic purposes. However, EMs exert adverse effects in the gastrointestinal, urinary, cardiovascular, and respiratory systems, which impede the development of EMs as new analgesics. Numerous studies have synthesized and investigated EM analogues and demonstrated that these EM derivatives had improved pharmacological properties, supporting their therapeutic perspectives. In the present review, the results of previous studies, particularly morphological and pharmacological studies, were summarized. Finally, EM modifications and their potential clinical implications were described. Applying this knowledge about EMs may provide information for further investigations in clinical application.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"98-116"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000484909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35548034","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":"Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats.","authors":"Changxing Wang,&nbsp;Chenglong Sun,&nbsp;Zhiying Hu,&nbsp;Xue Huo,&nbsp;Yang Yang,&nbsp;Xuehong Liu,&nbsp;Benson O A Botchway,&nbsp;Henry Davies,&nbsp;Marong Fang","doi":"10.1159/000471828","DOIUrl":"https://doi.org/10.1159/000471828","url":null,"abstract":"<p><strong>Background/aims: </strong>Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI). This study investigated the potential for poly (lactic-co-glycolic acid) (PLGA) complex inoculated with olfactory ensheathing cells (OECs) to treat spinal cord injury in a rat model.</p><p><strong>Methods: </strong>OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR) p75. The Basso, Beattie, and Bresnahan (BBB) score, together with an inclined plane (IP) test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB) staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP) and the microtubule-associated protein-2 (MAP-2), representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation.</p><p><strong>Results: </strong>The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05).</p><p><strong>Conclusion: </strong>PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000471828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34869893","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":"Increase of Substance P Concentration in Saliva after Pharyngeal Electrical Stimulation in Severely Dysphagic Stroke Patients - an Indicator of Decannulation Success?","authors":"Paul Muhle,&nbsp;Sonja Suntrup-Krueger,&nbsp;Stefan Bittner,&nbsp;Tobias Ruck,&nbsp;Inga Claus,&nbsp;Thomas Marian,&nbsp;Jens B Schröder,&nbsp;Jens Minnerup,&nbsp;Tobias Warnecke,&nbsp;Sven G Meuth,&nbsp;Rainer Dziewas","doi":"10.1159/000482002","DOIUrl":"https://doi.org/10.1159/000482002","url":null,"abstract":"<p><strong>Background/aims: </strong>Substance P (SP) is a neuropeptide, likely acting as a neurotransmitter in the pharyngeal mucosa enhancing the swallow and cough reflex. Pharyngeal Electrical Stimulation (PES) induces a temporary increase of salivary SP levels in healthy adults. Previous evidence suggests that post-stroke dysphagia is related to reduced SP levels. Here, we investigated the effects of PES on SP levels in severely dysphagic stroke patients and a possible link between increase of SP and treatment success.</p><p><strong>Methods: </strong>23 tracheotomized stroke patients who could not be decannulated due to severe and persisting dysphagia according to endoscopic evaluation received PES for 10 minutes a day over three consecutive days in this prospective single-center study. If initial treatment failed, repetitive stimulation cycles were provided. Saliva samples were collected before and directly after each PES.</p><p><strong>Results: </strong>61% of participants were decannulated after the first treatment cycle. Increase of SP levels post-stimulation was closely related to treatment success, i.e. decannulation with 79% of successfully treated patients showing increase of SP, whereas 89% of unsuccessfully treated patients had stable or decreased SP levels. Applying logistic regression analysis, increase of SP level remained the only independent predictor of decannulation after PES. All 3 repetitively treated patients showed increased SP levels when progressing from the 1st to the 2nd cycle, two of whom were decannulated hereafter.</p><p><strong>Conclusions: </strong>The physiological mechanism of PES may consist in restoration of sensory feedback, which is known to be crucial for the execution of a safe swallow. SP possibly acts as a biomarker for indicating response to PES.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"74-87"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000482002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35458859","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":"Blockade of Experimental Multiple Sclerosis by Inhibition of the Acid Sphingomyelinase/Ceramide System.","authors":"Katrin Anne Becker,&nbsp;Ramona Halmer,&nbsp;Laura Davies,&nbsp;Brian D Henry,&nbsp;Regan Ziobro-Henry,&nbsp;Yann Decker,&nbsp;Yang Liu,&nbsp;Erich Gulbins,&nbsp;Klaus Fassbender,&nbsp;Silke Walter","doi":"10.1159/000484621","DOIUrl":"https://doi.org/10.1159/000484621","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a severe and common autoimmune disorder of the central nervous system. Despite the availability of several novel treatment options, the disease is still poorly controlled, since the pathophysiological mechanisms are not fully understood.</p><p><strong>Methods: </strong>We tested the role of the acid sphingomyelinase/ceramide system in a model of MS, i.e. experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin-oligodendrocyte glycoprotein and the development of the disease was analyzed by histology, immunological tests and clinical assessment in wildtype and acid sphingomyelinase (Asm)-deficient mice.</p><p><strong>Results: </strong>Genetic deficiency of acid sphingomyelinase (Asm) protected against clinical symptoms in EAE and markedly attenuated the characteristic detrimental neuroinflammatory response. T lymphocyte adhesion, integrity of tight junctions, blood-brain barrier disruption and subsequent intracerebral infiltration of inflammatory cells were blocked in Asm-deficient mice after immunization. This resulted in an almost complete block of the development of disease symptoms in these mice, while wildtype mice showed severe neurological symptoms typical for EAE.</p><p><strong>Conclusion: </strong>Activation of the Asm/ceramide system is a central step for the development of EAE. Our findings may serve to identify novel therapeutic strategies for MS patients.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"88-97"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000484621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35247765","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":"Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells.","authors":"Elisa Venturini,&nbsp;Luigi Leanza,&nbsp;Michele Azzolini,&nbsp;Stephanie Kadow,&nbsp;Andrea Mattarei,&nbsp;Michael Weller,&nbsp;Ghazaleh Tabatabai,&nbsp;Michael J Edwards,&nbsp;Mario Zoratti,&nbsp;Cristina Paradisi,&nbsp;Ildikò Szabò,&nbsp;Erich Gulbins,&nbsp;Katrin Anne Becker","doi":"10.1159/000480643","DOIUrl":"https://doi.org/10.1159/000480643","url":null,"abstract":"<p><strong>Background/aims: </strong>Glioblastoma (GBM) is one of the most aggressive cancers, counting for a high number of the newly diagnosed patients with central nervous system (CNS) cancers in the United States and Europe. Major features of GBM include aggressive and invasive growth as well as a high resistance to treatment. Kv1.3, a potassium channel of the shaker family, is expressed in the inner mitochondrial membrane of many cancer cells. Inhibition of mitochondrial Kv1.3 was shown to induce apoptosis in several tumor cells at doses that were not lethal for normal cells.</p><p><strong>Methods: </strong>We investigated the expression of Kv1.3 in different glioma cell lines by immunocytochemistry, western blotting and electron microscopy and analyzed the effect of newly synthesized, mitochondria-targeted, Kv1.3 inhibitors on the induction of cell death in these cells. Finally, we performed in vivo studies on glioma bearing mice.</p><p><strong>Results: </strong>Here, we report that Kv1.3 is expressed in mitochondria of human and murine GL261, A172 and LN308 glioma cells. Treatment with the novel Kv1.3 inhibitors PAPTP or PCARBTP as well as with clofazimine induced massive cell death in glioma cells, while Psora-4 and PAP-1 were almost without effect. However, in vivo experiments revealed that the drugs had no effect on orthotopic brain tumors in vivo.</p><p><strong>Conclusion: </strong>These data serve as proof of principle that Kv1.3 inhibitors kills GBM cells, but drugs that act in vivo against glioblastoma must be developed to translate these findings in vivo.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"26-38"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000480643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35470502","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":"SGK3 Sensitivity of Large-Conductance Ca2+-Activated K+ Channel","authors":"Musaab Ahmed, Myriam Fezai, F. Lang","doi":"10.1159/000442618","DOIUrl":"https://doi.org/10.1159/000442618","url":null,"abstract":"Background/Aims: Large conductance Ca²⁺-activated K⁺ channels (maxi K⁺ channels or BK channels) are rapidly activated by increase of cytosolic Ca²⁺ activity. The channels participate in the regulation of diverse functions including neuronal excitation and cell volume. The BK channels may be modified by kinases. Channel regulating kinases include the serum & glucocorticoid inducible kinase 3 (SGK3). The present study explored whether SGK3 modifies the activity of BK channels. Methods: cRNA encoding the Ca²⁺ insensitive BK channel mutant BK^{M513I+Δ899-903} was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type SGK3, constitutively active ^S419DSGK3, or catalytically inactive ^K191NSGK3. K⁺ channel activity was measured utilizing dual electrode voltage clamp. Results: BK channel activity in BK^{M513I+Δ899-903} expressing oocytes was significantly increased by co-expression of SGK3 or active ^S419DSGK3, but not by coexpression of inactive ^K191NSGK3. Conclusion: SGK3 is a novel positive regulator of BK channels, and thus participates in the regulation of cell volume and excitability.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"113 - 124"},"PeriodicalIF":0.0,"publicationDate":"2016-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982608","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":"Cortical Responses and Shape Complexity of Stereoscopic Image - A Simultaneous EEG/MEG Study","authors":"Hohyun Cho, Min-Koo Kang, Sang-Kyun Ahn, Moonyoung Kwon, Kuk-jin Yoon, Kiwoong Kim, S. Jun","doi":"10.1159/000442617","DOIUrl":"https://doi.org/10.1159/000442617","url":null,"abstract":"Background/Aims: In exploring human factors, stereoscopic 3D images have been used to investigate the neural responses associated with excessive depth, texture complexity, and other factors. However, the cortical oscillation associated with the complexity of stereoscopic images has been studied rarely. Here, we demonstrated that the oscillatory responses to three differently shaped 3D images (circle, star, and bat) increase as the complexity of the image increases. Methods: We recorded simultaneous EEG/MEG for three different stimuli. Spatio-temporal and spatio-spectro-temporal features were investigated by non-parametric permutation test. Results: The results showed that N300 and alpha inhibition increased in the ventral area as the shape complexity of the stereoscopic image increased. Conclusion: It seems that the relative disparity in complex stereoscopic images may increase cognitive processing (N300) and cortical load (alpha inhibition) in the ventral area.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"102 - 112"},"PeriodicalIF":0.0,"publicationDate":"2016-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64983030","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 Regulates Tau Phosphorylation through Wnt Signaling Pathway in PC12 Cells","authors":"Zijuan Zhang, Meixia Guo, Juan Zhang, C. Du, Y. Xing","doi":"10.1159/000442616","DOIUrl":"https://doi.org/10.1159/000442616","url":null,"abstract":"Background/Aims: Leptin, an adipocytokine produced endogenously in the brain, is decreased in Alzheimer's disease(AD) and has also been shown to reduce Aβ levels in vitro and in vivo. Sets of evidence show that leptin reduces Aβ production and tau phosphorylation in neuronal cells and transgenic mice models of AD. Herein, we investigated the signaling pathway activated by leptin, to better understand its mechanism of action. Methods: Western blotting was performed to assess the levels of phosphor-tau and Bax, RT-PCR to check the mRNA level of Bax. Results: Leptin treatment significantly blunted Aβ-evoked tau phosphorylation and Bax levels, effects of which could be reversed by antagonist of Wnt signaling. Conclusion: The data indicate that Leptin may provide a novel therapeutic approach to AD treatment via wnt signaling.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"95 - 101"},"PeriodicalIF":0.0,"publicationDate":"2016-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64983023","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":"Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia","authors":"E. Masaki, K. Mizuta, N. Ohtani, K. Kido","doi":"10.1159/000442608","DOIUrl":"https://doi.org/10.1159/000442608","url":null,"abstract":"Background: Brain-derived neurotrophic factor (BDNF) from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. Results: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. Conclusion: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"15 - 24"},"PeriodicalIF":0.0,"publicationDate":"2016-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442608","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982985","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 Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy","authors":"S. Nase, S. Köhler, Jacqueline Jennebach, A. Eckert, N. Schweinfurth, J. Gallinat, U. Lang, S. Kühn","doi":"10.1159/000442607","DOIUrl":"https://doi.org/10.1159/000442607","url":null,"abstract":"Background: The predictive therapeutic value of brain derived neurotrophic factor (BDNF) and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. Methods: We examined serum BDNF (ELISA kit) in a sample of 76 (47 female and 29 male) depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA) was measured in the anterior cingulate cortex (ACC) with magnetic resonance spectroscopy (MRS). Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. Results: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. Limitations: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. Conclusion: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"1 - 14"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982915","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}