{"title":"Depressing interleukin-1β contributed to the synergistic effects of tramadol and minocycline on spinal nerve ligation-induced neuropathic pain.","authors":"Xiao-Peng Mei, Yasushi Sakuma, Cheng Xie, Dan Wu, Ichinyo Ho, Junichiro Kotani, Li-Xian Xu","doi":"10.1159/000355071","DOIUrl":"https://doi.org/10.1159/000355071","url":null,"abstract":"<p><p>Our previous study indicated that coadministration of tramadol and minocycline exerted synergistic effects on spinal nerve ligation (SNL)-induced neuropathic mechanical allodynia. However, the underlying mechanisms are still unclear. Recent reports indicated that spinal proinflammatory factor interleukin-1β (IL-1β) contributed to the development of neuropathic pain and the positive feedback communication between neuron and glia. Therefore, the present research is to confirm whether spinal IL-1β-related pathway response contributes to the synergistic effects of tramadol and minocycline on SNL-induced neuropathic pain. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn 3 days after lesion, which could be significantly decreased by tramadol and minocycline coadministration. Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication. Meanwhile, intrathecal administration of p38 inhibitor SB203580 markedly alleviated mechanical allodynia whilst reducing IL-1β and Fos expression induced by SNL. Moreover, intrathecal neutralized antibody of IL-1β could depress SNL-induced mechanical allodynia and Fos expression. These results suggest that depressing SNL-induced aberrant activation of the spinal dorsal horn IL-1β-related pathway contributes to the underlying mechanism of the synergistic effects of tramadol and minocycline coadministration on SNL-induced neuropathic mechanical allodynia.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":" ","pages":"30-42"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000355071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40264377","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}
NeurosignalsPub Date : 2014-01-01Epub Date: 2014-07-31DOI: 10.1159/000365290
Fanny C F Ip, Yu Pong Ng, H J An, Ying Dai, Hai Hong Pang, Yue Qing Hu, Allison C Chin, Calvin B Harley, Yung Hou Wong, Nancy Y Ip
{"title":"Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management.","authors":"Fanny C F Ip, Yu Pong Ng, H J An, Ying Dai, Hai Hong Pang, Yue Qing Hu, Allison C Chin, Calvin B Harley, Yung Hou Wong, Nancy Y Ip","doi":"10.1159/000365290","DOIUrl":"https://doi.org/10.1159/000365290","url":null,"abstract":"<p><p>Cycloastragenol (CAG) is an aglycone of astragaloside IV. It was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. The present study demonstrates that CAG stimulates telomerase activity and cell proliferation in human neonatal keratinocytes. In particular, CAG promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro. The distinct telomerase-activating property of CAG prompted evaluation of its potential application in the treatment of neurological disorders. Accordingly, CAG induced telomerase activity and cAMP response element binding (CREB) activation in PC12 cells and primary neurons. Blockade of CREB expression in neuronal cells by RNA interference reduced basal telomerase activity, and CAG was no longer efficacious in increasing telomerase activity. CAG treatment not only induced the expression of bcl2, a CREB-regulated gene, but also the expression of telomerase reverse transcriptase in primary cortical neurons. Interestingly, oral administration of CAG for 7 days attenuated depression-like behavior in experimental mice. In conclusion, CAG stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression. Furthermore, CAG may have a novel therapeutic role in depression.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"22 1","pages":"52-63"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000365290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32563024","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-02-23DOI: 10.1159/000334720
Olivia T W Ng, L W Chen, Y S Chan, Ken K L Yung
{"title":"Small interfering RNA specific for N-methyl-D-aspartate receptor 2B offers neuroprotection to dopamine neurons through activation of MAP kinase.","authors":"Olivia T W Ng, L W Chen, Y S Chan, Ken K L Yung","doi":"10.1159/000334720","DOIUrl":"https://doi.org/10.1159/000334720","url":null,"abstract":"<p><p>In the present study, N-methyl-D-aspartate receptor 2B (NR2B)-specific siRNA was applied in parkinsonian models. Our previous results showed that reduction in expression of N-methyl-D-aspartate receptor 1 (NR1), the key subunit of N-methyl-D-aspartate receptors, by antisense oligos ameliorated the motor symptoms in the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease (PD).</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 1-2","pages":"42-54"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000334720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30495592","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-09-07DOI: 10.1159/000338049
Xiao-Peng Mei, Lei Chen, Wei Wang, Dan Wu, Li-Ying Wang, Ting Zhang, Hui Zhang, Li-Xian Xu, Yun-Qing Li
{"title":"Combination of tramadol with minocycline exerted synergistic effects on a rat model of nerve injury-induced neuropathic pain.","authors":"Xiao-Peng Mei, Lei Chen, Wei Wang, Dan Wu, Li-Ying Wang, Ting Zhang, Hui Zhang, Li-Xian Xu, Yun-Qing Li","doi":"10.1159/000338049","DOIUrl":"https://doi.org/10.1159/000338049","url":null,"abstract":"<p><p>Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 3-4","pages":"184-96"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000338049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30894500","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-09-20DOI: 10.1159/000341980
Qian-Xing Zhuang, Yong-Hui Wu, Guan-Yi Wu, Jing-Ning Zhu, Jian-Jun Wang
{"title":"Histamine excites rat superior vestibular nuclear neurons via postsynaptic H1 and H2 receptors in vitro.","authors":"Qian-Xing Zhuang, Yong-Hui Wu, Guan-Yi Wu, Jing-Ning Zhu, Jian-Jun Wang","doi":"10.1159/000341980","DOIUrl":"https://doi.org/10.1159/000341980","url":null,"abstract":"<p><p>The superior vestibular nucleus (SVN), which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca(2+)/high-Mg(2+) medium, indicating a direct postsynaptic effect of the amine. Selective histamine H1 receptor agonist 2-pyridylethylamine and H2 receptor agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H1 receptor antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120, a selective H4 receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H1 and H2 instead of H4 receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H1 and H2 receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 3-4","pages":"174-83"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000341980","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30928902","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-05-09DOI: 10.1159/000336074
E M Kawamoto, C Scavone, M P Mattson, S Camandola
{"title":"Curcumin requires tumor necrosis factor α signaling to alleviate cognitive impairment elicited by lipopolysaccharide.","authors":"E M Kawamoto, C Scavone, M P Mattson, S Camandola","doi":"10.1159/000336074","DOIUrl":"https://doi.org/10.1159/000336074","url":null,"abstract":"<p><p>A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor α receptor 2 (TNFR2) signaling. In vivo, the ability of curcumin to counteract hippocampus-dependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl-D-aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 1-2","pages":"75-88"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000336074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30607449","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}
{"title":"The Golgi Apparatus: Panel Point of Cytosolic Ca(2+) Regulation.","authors":"Li-Hua Li, Xiang-Rong Tian, Zheng Jiang, Liu-Wang Zeng, Wen-Fang He, Zhi-Ping Hu","doi":"10.1159/000350471","DOIUrl":"https://doi.org/10.1159/000350471","url":null,"abstract":"<p><p>The Golgi apparatus (GA), an intermediate organelle of the cell inner membrane system, plays a key role in protein glycosylation and secretion. In recent years, this organelle has been found to act as a vital intracellular Ca(2+) store because different Ca (2+) regulators, such as the inositol-1,4,5-triphosphate receptor, sarco/endoplasmic reticulum Ca(2+) -ATPase and secretory pathway Ca 2+ -ATPase, were demonstrated to localize on their membrane. The mechanisms involved in Ca(2+) release and uptake in the GA have now been established.Here, based on careful backward looking on compartments and patterns in GA Ca (2+) regulation, we review neurological diseases related to GA calcium remodeling and propose a modified cytosolic Ca(2+) adjustment model, in which GA acts as part of the panel point.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 3-4","pages":"272-84"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000350471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31530064","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-05-09DOI: 10.1159/000337263
Man K Tse, Yung H Wong
{"title":"Neuronal functions of activators of G protein signaling.","authors":"Man K Tse, Yung H Wong","doi":"10.1159/000337263","DOIUrl":"https://doi.org/10.1159/000337263","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are one of the most important gateways for signal transduction across the plasma membrane. Over the past decade, several classes of alternative regulators of G protein signaling have been identified and reported to activate the G proteins independent of the GPCRs. One group of such regulators is the activator of G protein signaling (AGS) family which comprises of AGS1-10. They have entirely different activation mechanisms for G proteins as compared to the classic model of GPCR-mediated signaling and confer upon cells new avenues of signal transduction. As GPCRs are widely expressed in our nervous system, it is believed that the AGS family plays a major role in modulating the G protein signaling in neurons. In this article, we will review the current knowledge on AGS proteins in relation to their potential roles in neuronal regulations.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 3-4","pages":"259-71"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000337263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30605406","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-02-23DOI: 10.1159/000333296
Emma J Spary, Sally E Chapman, John K Sinfield, Azhar Maqbool, Jean Kaye, Trevor F C Batten
{"title":"Novel G protein-coupled oestrogen receptor GPR30 shows changes in mRNA expression in the rat brain over the oestrous cycle.","authors":"Emma J Spary, Sally E Chapman, John K Sinfield, Azhar Maqbool, Jean Kaye, Trevor F C Batten","doi":"10.1159/000333296","DOIUrl":"https://doi.org/10.1159/000333296","url":null,"abstract":"<p><p>Oestrogen influences autonomic function via actions at classical nuclear oestrogen receptors α and β in the brain, and recent evidence suggests the orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic oestrogen receptor. We investigated the expression of GPR30 in female rat brains throughout the oestrous cycle and after ovariectomy to determine whether GPR30 expression in central autonomic nuclei is correlated with circulating oestrogen levels. In the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM) and periaqueductal gray (PAG) GPR30 mRNA, quantified by real-time PCR, was increased in proestrus and oestrus. In ovariectomised (OVX) rats, expression in NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like immunoreactivity (GPR30-LI) colocalised with Golgi in neurones in many brain areas associated with autonomic pathways, and analysis of numbers of immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI was found in a variety of transmitter phenotypes, including cholinergic, serotonergic, catecholaminergic and nitrergic neurones in different neuronal groups. These observations support the view that GPR30 could act as a rapid transducer responding to oestrogen levels and thus modulate the activity of central autonomic pathways.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 1-2","pages":"14-27"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000333296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30496349","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}
NeurosignalsPub Date : 2013-01-01Epub Date: 2012-08-31DOI: 10.1159/000338020
C Heine, K Sygnecka, N Scherf, A Berndt, U Egerland, T Hage, H Franke
{"title":"Phosphodiesterase 2 inhibitors promote axonal outgrowth in organotypic slice co-cultures.","authors":"C Heine, K Sygnecka, N Scherf, A Berndt, U Egerland, T Hage, H Franke","doi":"10.1159/000338020","DOIUrl":"https://doi.org/10.1159/000338020","url":null,"abstract":"<p><p>The development of appropriate models assessing the potential of substances for regeneration of neuronal circuits is of great importance. Here, we present procedures to analyze effects of substances on fiber outgrowth based on organotypic slice co-cultures of the nigrostriatal dopaminergic system in combination with biocytin tracing and tyrosine hydroxylase labeling and subsequent automated image quantification. Selected phosphodiesterase inhibitors (PDE-Is) were studied to identify their potential growth-promoting capacities. Immunohistochemical methods were used to visualize developing fibers in the border region between ventral tegmental area/substantia nigra co-cultivated with the striatum as well as the cellular expression of PDE2A and PDE10. The quantification shows a significant increase of fiber density in the border region induced by PDE2-Is (BAY60-7550; ND7001), comparable with the potential of the nerve growth factor and in contrast to PDE10-I (MP-10). Analysis of tyrosine hydroxylase-positive fibers indicated a significant increase after treatment with BAY60-7550 and nerve growth factor in relation to dimethyl sulfoxide. Additionally, a dose-dependent increase of intracellular cGMP levels in response to the applied PDE2-Is in PDE2-transfected HEK293 cells was found. In summary, our findings show that PDE2-Is are able to significantly promote axonal outgrowth in organotypic slice co-cultures, which are a suitable model to assess growth-related effects in neuro(re)generation.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"21 3-4","pages":"197-212"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000338020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30881073","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}