Calcium ion (Ca 2+ ) has several physiological and pathophysiological functions such as communication, cell death and development in neurons. Normally, Ca 2+ concentration is too high in out of the neurons (1-3 mM) as compared to the inside of the neurons (50-100 nM). Ca 2+ passes the cell membranes through passive and active channels. Passive channels are leak channels. Well known active channels are including several channels such as voltage gated channels, chemical channels, store operated channels and mechanical channels (Kumar et al. 2014). In addition, Ca 2+ is released from intracellular organelles to cytosol by activation IP 3 and ryanodine receptors. Apart from the well-known cell membrane Ca 2+ channels, transient receptor potential (TRP) channels were discovered within the last decades. The TRP channels have 28 members within the 6 subgroups in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the well-known Ca 2+ channels. For example, TRP vanilloid 1 (TRPV1) channel is activated by hot chili pepper component (capsaicin), acidic pH, high temperature and the vanilloids ( Caterina et al. 1997). TRP melastatin 2 (TRPM2) channel is activated by ADP-Ribose and NAD + . TRPM2 and TRPV1 channels are also activated by oxidative stress ( Naziroglu and Braidy , 2017). In several neuronal diseases such as epilepsy and Alzheimer’s disease, intracellular free Ca 2+ concentration is increased by the oxidative stress. Hence, measurement of intracellular free Ca 2+ concentration is very important for discovering new calcium channel blocker drugs. In the cytosol of neurons, intracellular free Ca 2+ concentration was measured by using Ca 2+ indicators. There are two main classes of calcium indicators namely chemical indicators and genetically encoded calcium indicators. Chemical indicators of free intracellular Ca 2+ are Fura-2, Fluo-3, Fluo-4 and Rhod2. These dyes are often used with acetoxymethyl esters, in order to render the molecule lyphophlilic and to allow easy entrance into the cell. Genetically encoded indicators do not need to be loaded into cells, instead the genes encoding for these proteins can be easily transfected to cells. These indicators are fluorescent proteins derived from green fluorescent protein (GFP). In this presentation, I will summarize Ca 2+ signaling and using the fluorescent dyes for Ca 2+ imaging. In conclusion, intracellular free Ca 2+ concentration can be measured by using the indicators. In the measurement techniques, laser confocal microscopy seems best technique.
{"title":"Calcium signaling, TRP channels and intracellular Ca2+ measurement in neurons","authors":"M. Nazıroğlu","doi":"10.37212/JCNOS.583175","DOIUrl":"https://doi.org/10.37212/JCNOS.583175","url":null,"abstract":"Calcium ion (Ca 2+ ) has several physiological and pathophysiological functions such as communication, cell death and development in neurons. Normally, Ca 2+ concentration is too high in out of the neurons (1-3 mM) as compared to the inside of the neurons (50-100 nM). Ca 2+ passes the cell membranes through passive and active channels. Passive channels are leak channels. Well known active channels are including several channels such as voltage gated channels, chemical channels, store operated channels and mechanical channels (Kumar et al. 2014). In addition, Ca 2+ is released from intracellular organelles to cytosol by activation IP 3 and ryanodine receptors. Apart from the well-known cell membrane Ca 2+ channels, transient receptor potential (TRP) channels were discovered within the last decades. The TRP channels have 28 members within the 6 subgroups in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the well-known Ca 2+ channels. For example, TRP vanilloid 1 (TRPV1) channel is activated by hot chili pepper component (capsaicin), acidic pH, high temperature and the vanilloids ( Caterina et al. 1997). TRP melastatin 2 (TRPM2) channel is activated by ADP-Ribose and NAD + . TRPM2 and TRPV1 channels are also activated by oxidative stress ( Naziroglu and Braidy , 2017). In several neuronal diseases such as epilepsy and Alzheimer’s disease, intracellular free Ca 2+ concentration is increased by the oxidative stress. Hence, measurement of intracellular free Ca 2+ concentration is very important for discovering new calcium channel blocker drugs. In the cytosol of neurons, intracellular free Ca 2+ concentration was measured by using Ca 2+ indicators. There are two main classes of calcium indicators namely chemical indicators and genetically encoded calcium indicators. Chemical indicators of free intracellular Ca 2+ are Fura-2, Fluo-3, Fluo-4 and Rhod2. These dyes are often used with acetoxymethyl esters, in order to render the molecule lyphophlilic and to allow easy entrance into the cell. Genetically encoded indicators do not need to be loaded into cells, instead the genes encoding for these proteins can be easily transfected to cells. These indicators are fluorescent proteins derived from green fluorescent protein (GFP). In this presentation, I will summarize Ca 2+ signaling and using the fluorescent dyes for Ca 2+ imaging. In conclusion, intracellular free Ca 2+ concentration can be measured by using the indicators. In the measurement techniques, laser confocal microscopy seems best technique.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46290273","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}
Chemotherapeutic agents such as cisplatin and 5fluorouracil are very effective and commonly used chemotherapeutic agents in treatment of several cancers including breast, testicular, ovarian and lung cancers. However, they have adverse effects and apoptosis in normal cells and neurons including optic nerve (Cardellicchio et al. 2014). Oxidative stress occurs during the several physiological functions such as mitochondria and phagocytosis. If the products of oxidative stress such as superoxide radical and hydrogen peroxide will be controlled by antioxidants the cell injury in normal tissue will not be occur. Results of recent reports indicated that optic nerve injury was induced through excessive production of reactive oxygen species (ROS) in rats by chemotherapeutic agents, although ROS were scavenged by antioxidants such as pycnogenol and rutin (Icel et al. 2018; Tasli et al. 2018). It seems that the chemotherapeutic agentsinduced excessive ROS production results in increased levels of lipid peroxidation as malondialdehyde and inflammation markers such as TNF-α and NF-κB levels, but decrease of glutathione and total antioxidant levels. Apoptosis in the optic nerve was induced in ARPE19 eye cells by activation of intrinsic apoptosis pathway and death receptor signaling (Guclu et al. 2018). In the presentation, we discussed novel effects of oxidative stress and apoptosis on the optic nerve injury in rodentsand human. The results of current data suggest that oxidative stress has a main role in chemotherapeutic agentsinduced optic nerve injury in rodents, although the injury was attenuated by the antioxidant treatment.
化疗药物如顺铂和5氟尿嘧啶是治疗乳腺癌、睾丸癌、卵巢癌和肺癌等几种癌症的非常有效和常用的化疗药物。然而，它们在正常细胞和包括视神经在内的神经元中有不良反应和凋亡(Cardellicchio et al. 2014)。氧化应激发生在线粒体和吞噬等多种生理功能中。如果超氧自由基、过氧化氢等氧化应激产物被抗氧化剂控制，正常组织的细胞损伤就不会发生。最近的研究结果表明，化疗药物在大鼠体内过量产生活性氧(ROS)诱导视神经损伤，尽管ROS可以被碧萝酚和芦丁等抗氧化剂清除(Icel et al. 2018;Tasli et al. 2018)。似乎化疗药物诱导的过量ROS产生导致丙二醛等脂质过氧化水平和炎症标志物如TNF-α和NF-κB水平升高，但谷胱甘肽和总抗氧化剂水平降低。ARPE19眼细胞通过激活内在凋亡通路和死亡受体信号传导诱导视神经凋亡(Guclu et al. 2018)。在报告中，我们讨论了氧化应激和细胞凋亡在啮齿动物和人类视神经损伤中的新作用。目前的研究结果表明，氧化应激在化疗药物诱导的啮齿动物视神经损伤中起主要作用，尽管抗氧化处理能减轻损伤。
{"title":"Chemotherapeutic agents increase mitochondrial oxidative stress and apoptosis in optic nerve","authors":"Dilek Özkaya, M. Nazıroğlu","doi":"10.37212/JCNOS.584709","DOIUrl":"https://doi.org/10.37212/JCNOS.584709","url":null,"abstract":"Chemotherapeutic agents such as cisplatin and 5fluorouracil are very effective and commonly used chemotherapeutic agents in treatment of several cancers including breast, testicular, ovarian and lung cancers. However, they have adverse effects and apoptosis in normal cells and neurons including optic nerve (Cardellicchio et al. 2014). Oxidative stress occurs during the several physiological functions such as mitochondria and phagocytosis. If the products of oxidative stress such as superoxide radical and hydrogen peroxide will be controlled by antioxidants the cell injury in normal tissue will not be occur. Results of recent reports indicated that optic nerve injury was induced through excessive production of reactive oxygen species (ROS) in rats by chemotherapeutic agents, although ROS were scavenged by antioxidants such as pycnogenol and rutin (Icel et al. 2018; Tasli et al. 2018). It seems that the chemotherapeutic agentsinduced excessive ROS production results in increased levels of lipid peroxidation as malondialdehyde and inflammation markers such as TNF-α and NF-κB levels, but decrease of glutathione and total antioxidant levels. Apoptosis in the optic nerve was induced in ARPE19 eye cells by activation of intrinsic apoptosis pathway and death receptor signaling (Guclu et al. 2018). In the presentation, we discussed novel effects of oxidative stress and apoptosis on the optic nerve injury in rodentsand human. The results of current data suggest that oxidative stress has a main role in chemotherapeutic agentsinduced optic nerve injury in rodents, although the injury was attenuated by the antioxidant treatment.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42191195","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}
Glia constitutes a heterogeneous cell population that makes up half of the cells in the central nervous system (CNS). Glial cells include macroglia, astrocytes and oligodendrocytes, and microglia. Their roles are very diverse but overall they orchestrate CNS formation and function by providing neurons with essential support. Although glia-derived immortalized cell lines are now available, primary cultures of glial cells still constitute the most reliable method to study glial functions as the primary cultures retain important characteristics and markers of glia from their normal brain environment. Isolation and culturing of glia from postnatal rodent brain is well-characterized and give higher yield than from adult brain. Therefore, isolation of glial cells from postnatal mouse brains, with an emphasis on microglia, will be described. It will include a protocol describing the steps of isolation and necessary equipments and reagents, as well as the subsequent cell culture monitoring and potential applications.
{"title":"Isolation of glia from mice","authors":"S. Derouiche","doi":"10.37212/JCNOS.584618","DOIUrl":"https://doi.org/10.37212/JCNOS.584618","url":null,"abstract":"Glia constitutes a heterogeneous cell population that makes up half of the cells in the central nervous system (CNS). Glial cells include macroglia, astrocytes and oligodendrocytes, and microglia. Their roles are very diverse but overall they orchestrate CNS formation and function by providing neurons with essential support. Although glia-derived immortalized cell lines are now available, primary cultures of glial cells still constitute the most reliable method to study glial functions as the primary cultures retain important characteristics and markers of glia from their normal brain environment. Isolation and culturing of glia from postnatal rodent brain is well-characterized and give higher yield than from adult brain. Therefore, isolation of glial cells from postnatal mouse brains, with an emphasis on microglia, will be described. It will include a protocol describing the steps of isolation and necessary equipments and reagents, as well as the subsequent cell culture monitoring and potential applications.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41956141","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}
As a complex problem, pain activates several conditions, symptoms, and molecular pathways. After stimulation of a nociceptors, action potentials are generated and then propagated to the brain, resulting in a sensation of pain is induces through production and propagation of action potential. Most efficient way to treat chronic pain is with opioids, however the drugs of opioid system induce several adverse effects such as addictive behavior and desensitization. Chemotherapeutic agent (such as oxaliplatin, cisplatin, paclitaxel)-based anticancer drugs cause neurotoxicity through excessive calcium ion (Ca2+) influx. Peripheral neuropathies are a common side effect of treatment of various chemotherapeutics. Today, targeting the cation channels and excessive Ca2+ influx that contribute to the detection of stimuli may be an effective approach in treating chemotherapeutic agents-induced pain syndromes. Several physiological and pathophysiological functions are induced by excessive Ca2+ influx. The Ca2+ passes the cell membrane through several channels such as voltage gated calcium channels (VGCC) and chemical (ligand) channels. In addition to the well-known VGCC and ligand channel, new channels namely transient receptor potential (TRP) channels were discovered within last decades. The TRP superfamily is including 28 members in mammalian and a member of the TRP superfamily is TRP vanilloid 1 (TRPV1) channels. The TRPV1 channel is activated by several stimuli including hot chili pepper component (capsaicin), heat, acidic pH and oxidative stress (Caterina et al. 1997). Expression levels of TRPV1 channel is high in dorsal root ganglion (DRG) and it is mainly responsible from neuropathic pain (Naziroglu and Braidy, 2017; Muller et al. 2019). Therefore, TRPV1 channel has great importance in the chemotherapy-induced neuropathic pain induction. In the current study, I will summarize present reports on the TRPV1 channel in literature. as novel target for treating chemotherapy-induced peripheral pain. In addition, I will summarize future directions of the novel targets.
{"title":"Interactions between chemotherapy-induced neuropathic pain and TRPV1 channel","authors":"Hacı Ömer Osmanlioğlu","doi":"10.37212/JCNOS.584691","DOIUrl":"https://doi.org/10.37212/JCNOS.584691","url":null,"abstract":"As a complex problem, pain activates several conditions, symptoms, and molecular pathways. After stimulation of a nociceptors, action potentials are generated and then propagated to the brain, resulting in a sensation of pain is induces through production and propagation of action potential. Most efficient way to treat chronic pain is with opioids, however the drugs of opioid system induce several adverse effects such as addictive behavior and desensitization. Chemotherapeutic agent (such as oxaliplatin, cisplatin, paclitaxel)-based anticancer drugs cause neurotoxicity through excessive calcium ion (Ca2+) influx. Peripheral neuropathies are a common side effect of treatment of various chemotherapeutics. Today, targeting the cation channels and excessive Ca2+ influx that contribute to the detection of stimuli may be an effective approach in treating chemotherapeutic agents-induced pain syndromes. Several physiological and pathophysiological functions are induced by excessive Ca2+ influx. The Ca2+ passes the cell membrane through several channels such as voltage gated calcium channels (VGCC) and chemical (ligand) channels. In addition to the well-known VGCC and ligand channel, new channels namely transient receptor potential (TRP) channels were discovered within last decades. The TRP superfamily is including 28 members in mammalian and a member of the TRP superfamily is TRP vanilloid 1 (TRPV1) channels. The TRPV1 channel is activated by several stimuli including hot chili pepper component (capsaicin), heat, acidic pH and oxidative stress (Caterina et al. 1997). Expression levels of TRPV1 channel is high in dorsal root ganglion (DRG) and it is mainly responsible from neuropathic pain (Naziroglu and Braidy, 2017; Muller et al. 2019). Therefore, TRPV1 channel has great importance in the chemotherapy-induced neuropathic pain induction. In the current study, I will summarize present reports on the TRPV1 channel in literature. as novel target for treating chemotherapy-induced peripheral pain. In addition, I will summarize future directions of the novel targets.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44631184","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}
Retina is a part of central nervous system. Retinal degeneration is characterized by the death of photoreceptor cells, causing partial vision loss or even blindness. Retinal degeneration includes inherited retinal degeneration such as retinitis pigmentosa (RP) and complex retinal degeneration such as diabetic retinopathy. In this talk, I will discuss the disease mechanisms and current treatment of inherited retinal degeneration. I will also discuss techniques for retinal degeneration in mouse models. I will demonstrate how to dissect mouse retina and retinal pigment epithelial (RPE) cells.
{"title":"Mouse models for retinal degeneration","authors":"X. Shu","doi":"10.37212/JCNOS.584625","DOIUrl":"https://doi.org/10.37212/JCNOS.584625","url":null,"abstract":"Retina is a part of central nervous system. Retinal degeneration is characterized by the death of photoreceptor cells, causing partial vision loss or even blindness. Retinal degeneration includes inherited retinal degeneration such as retinitis pigmentosa (RP) and complex retinal degeneration such as diabetic retinopathy. In this talk, I will discuss the disease mechanisms and current treatment of inherited retinal degeneration. I will also discuss techniques for retinal degeneration in mouse models. I will demonstrate how to dissect mouse retina and retinal pigment epithelial (RPE) cells.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46261761","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}
Incidence of multiple sclerosis (MS) is increasing over all the world, because effective treatment of the disease has not been discovered yet. In the treatment of MS, different inflammatory chemical drugs have been used, but they have adverse effects on the normal cells and neurons, although plant extracts including Hypericum perforatum has no adverse effects on the normal cells in human. Oxidative stress induced excessive production of reactive oxygen species (ROS) and ROS production occurs during the several physiological and pathophysiological functions. Hypericum perforatum known as St. John’s Wort, has been proven to relieve in depression. However, results of recent studies reported modulator role of Hypericum perforatum on MS in rats (Naziroglu et al. 2014). The cellular and molecular mechanisms that underlie the effects of the Hypericum perforatum on MS pain pathways are not known, results in the literature suggest that the modulator effects of Hypericum perforatum in MS could be related to an increase antioxidant effect (Mojaverrostami et al. 2018). Recently, modulator roles of plant extracts such as Hypericum perforatum and through inhibition of ROS production in the treatment of MS have been reported. However, antioxidant contents of the plant extracts were affected by several factors, including extraction procedures (Dresler et al. 2018). In the presentation, I will review current data on the extraction procedures of Hypericum perforatum. In addition, I will summarize recent data on therapeutic roles of Hypericum perforatum in MS. In conclusion, it seems that Hypericum perforatum has potential therapeutic effects against MS-induced oxidative stress.
{"title":"The protective role of Hypericum perforatum in treatment of oxidative stress-induced multiple sclerosis is affected by extraction procedure: A literature review","authors":"Tunhan Demirci","doi":"10.37212/JCNOS.584706","DOIUrl":"https://doi.org/10.37212/JCNOS.584706","url":null,"abstract":"Incidence of multiple sclerosis (MS) is increasing over all the world, because effective treatment of the disease has not been discovered yet. In the treatment of MS, different inflammatory chemical drugs have been used, but they have adverse effects on the normal cells and neurons, although plant extracts including Hypericum perforatum has no adverse effects on the normal cells in human. Oxidative stress induced excessive production of reactive oxygen species (ROS) and ROS production occurs during the several physiological and pathophysiological functions. Hypericum perforatum known as St. John’s Wort, has been proven to relieve in depression. However, results of recent studies reported modulator role of Hypericum perforatum on MS in rats (Naziroglu et al. 2014). The cellular and molecular mechanisms that underlie the effects of the Hypericum perforatum on MS pain pathways are not known, results in the literature suggest that the modulator effects of Hypericum perforatum in MS could be related to an increase antioxidant effect (Mojaverrostami et al. 2018). Recently, modulator roles of plant extracts such as Hypericum perforatum and through inhibition of ROS production in the treatment of MS have been reported. However, antioxidant contents of the plant extracts were affected by several factors, including extraction procedures (Dresler et al. 2018). In the presentation, I will review current data on the extraction procedures of Hypericum perforatum. In addition, I will summarize recent data on therapeutic roles of Hypericum perforatum in MS. In conclusion, it seems that Hypericum perforatum has potential therapeutic effects against MS-induced oxidative stress.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46529313","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}
Microglial cell is a highly plastic cell in which it retracts its branched processes upon activation by structurally diverse molecules. Elevation of these molecules in the brain has been implicated in a diversity of diseases conditions in the CNS, where these molecules promote production of toxicity mediators, such as ROS. Microglial cell activation in response to ROS has been of particular interest. Emerging evidence supports a role for the TRPM2 channel in ROS-induced neuroinflammation. Thus, the current study aims to examine the role of the TRPM2 channel in mediating H2O2-induced microglial activation. A multidisciplinary approach was adopted, including primary microglial isolation, single cell calcium imaging, immunocytochemistry, confocal microscopy and computer-aided analysis of cell morphology. H2O2-induced microglial activation were observed in WT microglial cells but were ablated by genetic or pharmacological inhibition of the TRPM2 channel. Exposure to H2O2 raised the [Ca2+]i via promoting Ca2+ influx, which was prevented by TRPM2-KO. H2O2 induced ROS production and PARP-1 activation. H2O2induced ROS production and PARP-1 activation as well as an increase in the [Ca2+]i and microglial activation, were suppressed by inhibiting PKC and NOX. Furthermore, H2O2-induced PARP-1 activation, increase in the [Ca2+]i and microglial activation were attenuated by inhibiting the Ca2+-sensitive PYK2 and downstream MEK/ERK kinases. The findings provide strong evidence to support that the TRPM2 channel is functionally expressed and plays a major role in ROS-induced Ca2+ signalling as well as cell activation in microglia. Such information is useful for a better understanding of microglial cells in oxidative stress-related pathologies.
{"title":"Signalling mechanisms for ROS-induced TRPM2 mediated microglial cell activation","authors":"Sharifah Alawieyah Syed Mortadza, Lin-Hua Jiang","doi":"10.37212/JCNOS.584717","DOIUrl":"https://doi.org/10.37212/JCNOS.584717","url":null,"abstract":"Microglial cell is a highly plastic cell in which it retracts its branched processes upon activation by structurally diverse molecules. Elevation of these molecules in the brain has been implicated in a diversity of diseases conditions in the CNS, where these molecules promote production of toxicity mediators, such as ROS. Microglial cell activation in response to ROS has been of particular interest. Emerging evidence supports a role for the TRPM2 channel in ROS-induced neuroinflammation. Thus, the current study aims to examine the role of the TRPM2 channel in mediating H2O2-induced microglial activation. A multidisciplinary approach was adopted, including primary microglial isolation, single cell calcium imaging, immunocytochemistry, confocal microscopy and computer-aided analysis of cell morphology. H2O2-induced microglial activation were observed in WT microglial cells but were ablated by genetic or pharmacological inhibition of the TRPM2 channel. Exposure to H2O2 raised the [Ca2+]i via promoting Ca2+ influx, which was prevented by TRPM2-KO. H2O2 induced ROS production and PARP-1 activation. H2O2induced ROS production and PARP-1 activation as well as an increase in the [Ca2+]i and microglial activation, were suppressed by inhibiting PKC and NOX. Furthermore, H2O2-induced PARP-1 activation, increase in the [Ca2+]i and microglial activation were attenuated by inhibiting the Ca2+-sensitive PYK2 and downstream MEK/ERK kinases. The findings provide strong evidence to support that the TRPM2 channel is functionally expressed and plays a major role in ROS-induced Ca2+ signalling as well as cell activation in microglia. Such information is useful for a better understanding of microglial cells in oxidative stress-related pathologies.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46809155","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}
Several physiological and pathophysiological functions such as mitochondria and phagocytosis induce oxidative stress. Oxidative stress results in excessive production of reactive oxygen species (ROS). There is a high amount of psychologically and chemically stress in in vitro fertilization (IVF), because of presence stressful permanent infertility and treatment procedures (An et al. 2013). Oocytes are surrounded by granulosa cells. It is well-known that there is a direct relationship between oxidative stress contents of granulosa cells and oocyte quality (Tola et al 2013). Excessive Ca2+ influx induces excessive mitochondrial ROS production and apoptosis through activation of caspase activations. Involvement of voltage gated Ca2+ channels on oocyte quality and apoptosis in the granulosa cells has been clarified by results of several studies (Platano et al. 2013; Tola et al 2013). Transient receptor potential vanilloid 1 (TRPV1) channel is a calcium permeable and non-selective cation channel. The similar effects of voltage gated calcium channels may present between oxidative stress and TRPV1 channel activation in the oocyte, because the TRPV1 channel is activated by excessive production of ROS. The importance of TRPV1 channel on the oocyte maturation was recently reported (Cecconi et al. 2019). In the oral presentation, I will review recent studies on apoptosis through TRPV1 channel activation in granulosa cells of oocyte during IVF. In conclusion, current literature data indicated that psychological and oxidative stress-induced ROS, apoptosis and Ca2+ contents of oocyte and granulosa cells have very important roles on the oocyte maturation in patients with infertility during the IVF. There are some involvement clues of TRPV1 channels on the oocyte maturation and apoptosis, but the subject needs future studies.
一些生理和病理生理功能，如线粒体和吞噬作用诱导氧化应激。氧化应激导致活性氧(ROS)的过量产生。体外受精(IVF)中存在大量的心理和化学压力，因为存在永久性不孕和治疗过程的压力(An et al. 2013)。卵母细胞被颗粒细胞包围。众所周知，颗粒细胞氧化应激含量与卵母细胞质量之间存在直接关系(Tola et al . 2013)。过量的Ca2+内流通过激活caspase激活诱导过量的线粒体ROS产生和凋亡。电压门控Ca2+通道对卵母细胞质量和颗粒细胞凋亡的影响已经被几项研究的结果所阐明(Platano et al. 2013;Tola et al . 2013)。瞬时受体电位香草蛋白1 (TRPV1)通道是一种钙渗透性非选择性阳离子通道。电压门控钙通道的类似作用可能存在于氧化应激和卵母细胞中TRPV1通道激活之间，因为TRPV1通道被ROS的过量产生激活。最近报道了TRPV1通道对卵母细胞成熟的重要性(Cecconi et al. 2019)。在口头报告中，我将回顾IVF过程中卵母细胞颗粒细胞通过TRPV1通道激活凋亡的最新研究。综上所述，目前的文献资料表明，心理和氧化应激诱导的卵母细胞和颗粒细胞的ROS、凋亡和Ca2+含量对体外受精不孕患者卵母细胞成熟有非常重要的作用。TRPV1通道参与卵母细胞成熟和凋亡有一定线索，有待进一步研究。
{"title":"Psychological and oxidative stress induce apoptosis through TRPV1 channel activation in granulosa cells of oocyte during in vitro fertilization","authors":"D. U. Karatopuk","doi":"10.37212/JCNOS.584712","DOIUrl":"https://doi.org/10.37212/JCNOS.584712","url":null,"abstract":"Several physiological and pathophysiological functions such as mitochondria and phagocytosis induce oxidative stress. Oxidative stress results in excessive production of reactive oxygen species (ROS). There is a high amount of psychologically and chemically stress in in vitro fertilization (IVF), because of presence stressful permanent infertility and treatment procedures (An et al. 2013). Oocytes are surrounded by granulosa cells. It is well-known that there is a direct relationship between oxidative stress contents of granulosa cells and oocyte quality (Tola et al 2013). Excessive Ca2+ influx induces excessive mitochondrial ROS production and apoptosis through activation of caspase activations. Involvement of voltage gated Ca2+ channels on oocyte quality and apoptosis in the granulosa cells has been clarified by results of several studies (Platano et al. 2013; Tola et al 2013). Transient receptor potential vanilloid 1 (TRPV1) channel is a calcium permeable and non-selective cation channel. The similar effects of voltage gated calcium channels may present between oxidative stress and TRPV1 channel activation in the oocyte, because the TRPV1 channel is activated by excessive production of ROS. The importance of TRPV1 channel on the oocyte maturation was recently reported (Cecconi et al. 2019). In the oral presentation, I will review recent studies on apoptosis through TRPV1 channel activation in granulosa cells of oocyte during IVF. In conclusion, current literature data indicated that psychological and oxidative stress-induced ROS, apoptosis and Ca2+ contents of oocyte and granulosa cells have very important roles on the oocyte maturation in patients with infertility during the IVF. There are some involvement clues of TRPV1 channels on the oocyte maturation and apoptosis, but the subject needs future studies.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41378655","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}
Epilepsy is a disorder of the brain, characterized by an enduring predisposition for the generation of epileptic seizures because of hyperexcitability and hypersynchrony of cortical neurons (Devinsky et al. 2014). Salmon calcitonin is a type of calcitonin with 32 amino acids. It is more potency than human calcitonin due to differences in its amino acid sequence (Masi et al. 2007). In the current study, we investigated the effects of salmon calcitonin on pentylenetetrazoleinduced seizures in kindled rats. In our study, 48 (240-260 g) male Wistar Albino rats were used. Rats were kindled by injections of a subconvulsant dose of pentylenetetrazole (35 mg/kg) once every other day for 15 times. Epileptic behaviors were observed for a period of 30 min. Seizure activity was scored, using the revised Racine’s scale. Rats that had seizure stages of 4 or 5 after three consecutive injections of PTZ were defined as fully kindled. The kindled rats were divided into six groups (n=8 for each group) as saline (1 ml/kg saline), salmon calcitonin (25, 50 and 100 µg/kg), ethosuximide (100 mg/kg) and ethosuximide + salmon calcitonin. Electrodes were placed to animals’ skulls under stereotaxy to receive electroencephalography (EEG). After thirty minutes of administration of drugs, 35 mg/kg PTZ was given to induce seizures. EEG and video recordings of animals were taken simultaneously for thirty minutes. In the evaluation of the video and EEG recordings, the seizure stages of animals, the first myoclonic jerk time and the number of epileptic seizure spikes were calculated. Salmon calcitonin reduced seizures stage, epileptic seizure spikes and also prolonged first myoclonic jerk time compared to saline group. In addition, salmon calcitonin and ethosuximide combination decreased epileptic seizure spikes and increased the first myoclonic jerk time compare to ethosuximide group. In conclusion, salmon calcitonin decreased epileptic seizures and improved anticonvulsant effect of ethosuximide in the pentylentetrazole-kindled rat.
{"title":"The anticonvulsant effects of salmon calcitonin on pentylenetetrazole-kindled rats","authors":"A. Taskiran, E. Ozdemir","doi":"10.37212/JCNOS.584705","DOIUrl":"https://doi.org/10.37212/JCNOS.584705","url":null,"abstract":"Epilepsy is a disorder of the brain, characterized by an enduring predisposition for the generation of epileptic seizures because of hyperexcitability and hypersynchrony of cortical neurons (Devinsky et al. 2014). Salmon calcitonin is a type of calcitonin with 32 amino acids. It is more potency than human calcitonin due to differences in its amino acid sequence (Masi et al. 2007). In the current study, we investigated the effects of salmon calcitonin on pentylenetetrazoleinduced seizures in kindled rats. In our study, 48 (240-260 g) male Wistar Albino rats were used. Rats were kindled by injections of a subconvulsant dose of pentylenetetrazole (35 mg/kg) once every other day for 15 times. Epileptic behaviors were observed for a period of 30 min. Seizure activity was scored, using the revised Racine’s scale. Rats that had seizure stages of 4 or 5 after three consecutive injections of PTZ were defined as fully kindled. The kindled rats were divided into six groups (n=8 for each group) as saline (1 ml/kg saline), salmon calcitonin (25, 50 and 100 µg/kg), ethosuximide (100 mg/kg) and ethosuximide + salmon calcitonin. Electrodes were placed to animals’ skulls under stereotaxy to receive electroencephalography (EEG). After thirty minutes of administration of drugs, 35 mg/kg PTZ was given to induce seizures. EEG and video recordings of animals were taken simultaneously for thirty minutes. In the evaluation of the video and EEG recordings, the seizure stages of animals, the first myoclonic jerk time and the number of epileptic seizure spikes were calculated. Salmon calcitonin reduced seizures stage, epileptic seizure spikes and also prolonged first myoclonic jerk time compared to saline group. In addition, salmon calcitonin and ethosuximide combination decreased epileptic seizure spikes and increased the first myoclonic jerk time compare to ethosuximide group. In conclusion, salmon calcitonin decreased epileptic seizures and improved anticonvulsant effect of ethosuximide in the pentylentetrazole-kindled rat.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49402965","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}
Our ability to perceive nociceptive pain is crucial to respond to harmful stimuli: it warns us about noxiously hot or cold objects. Sensory nerve endings that respond to pain (nociceptors) initiate an electrical signal in the periphery and transport it to the dorsal horn and eventually to higher brain centers. The detection of noxious stimuli involves the expression of nociceptive ion channels in sensory nerve endings, such as transient receptor potential (TRP) channels. Recently we found that the acute response to noxious heat relies on the functional expression of TRPV1, TRPM3 and TRPA1 in sensory nerve endings. Calcium imaging on isolated dorsal root ganglia (DRG) is a widely accepted model to study the involvement of TRP channels in acute pain responses. However, DRGs are clusters of nerve cell bodies, present in the dorsal root of spinal nerves, far away from the skin where the physiological stimulus detection take place. We use two different optical measurement protocols to study ion channel activity in sensory neurons: an in vivo-protocol to image DRGs and an in tissue-protocol to visualize intact skin measurements. A cre-dependent GCaMP3 mouse line is used. These mice express the genetically encoded calcium indicator GCaMP3 in specific somatosensory neurons. Using this technique, we study the role of TRP channels in different pain models, such as inflammation.
{"title":"In vivo and ex vivo imaging of nociceptor expression and activity","authors":"Marie Mulier, J. Vriens, T. Voets","doi":"10.37212/JCNOS.584620","DOIUrl":"https://doi.org/10.37212/JCNOS.584620","url":null,"abstract":"Our ability to perceive nociceptive pain is crucial to respond to harmful stimuli: it warns us about noxiously hot or cold objects. Sensory nerve endings that respond to pain (nociceptors) initiate an electrical signal in the periphery and transport it to the dorsal horn and eventually to higher brain centers. The detection of noxious stimuli involves the expression of nociceptive ion channels in sensory nerve endings, such as transient receptor potential (TRP) channels. Recently we found that the acute response to noxious heat relies on the functional expression of TRPV1, TRPM3 and TRPA1 in sensory nerve endings. Calcium imaging on isolated dorsal root ganglia (DRG) is a widely accepted model to study the involvement of TRP channels in acute pain responses. However, DRGs are clusters of nerve cell bodies, present in the dorsal root of spinal nerves, far away from the skin where the physiological stimulus detection take place. We use two different optical measurement protocols to study ion channel activity in sensory neurons: an in vivo-protocol to image DRGs and an in tissue-protocol to visualize intact skin measurements. A cre-dependent GCaMP3 mouse line is used. These mice express the genetically encoded calcium indicator GCaMP3 in specific somatosensory neurons. Using this technique, we study the role of TRP channels in different pain models, such as inflammation.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42350692","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}
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