Accumulating evidences have indicated that disturbances in intracellular free calcium ([Ca2+]i) concentration play an important role in the pathophysiology of peripheral pain. Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. At least, 11 TRP channels in mammalian cells have been identified as thermosensitive TRP (thermo-TRP) channels (Uchida et al. 2017). Two TRP channels (TRPV1 and TRPV2) are activated by high temperatures. Five TRP channels (TRPV1-4 and TRPM2) are activated by different heat temperatures, although two of TRP channels (TRPA1 and TRPM8) are activated by cold and cool temperatures, respectively (Naziroglu and Braidy, 2017). It is well known that increase of [Ca2+]i concentration but decrease of intracellular Mg2+ levels induces activation of nitric oxide synthase (NOS) enzyme. By catalytic activity of NOS, nitric oxide synthetizes in neurons. In turn, it induces pain through production of excitatory amino acids and substance P (Medvedeva et al. 2008). Results of recent studies indicated involvement of chemothrepeutic agents (i.e. cisplatin, oxaliplatin and paclitaxel)-induced mitochondrial oxidative stress through activation of Thermo TRP channels such as TRPA1, TRPV1 and TRPM8, although antioxidants induced protective action on the pain induction through inhibition of the TRP channels in the experimental animals (Materazzi et al. 2012). In the oral presentation, I discussed novel effects of chemotherapeutic agents on the peripheral pain by the regulation of TRP channels. I concluded that the chemotherapeutic agents cause TRP channel activation and oxidative stress, which may lead to the pathology of peripheral pain. It seems to that the exact relationship between TRP channel activation and chemotherapeutic agents still remain to be determined.
{"title":"Involvement of Thermo TRP channels on chemothrepeutic agents-induced peripheral pain","authors":"M. K. Yıldırım","doi":"10.37212/jcnos.610118","DOIUrl":"https://doi.org/10.37212/jcnos.610118","url":null,"abstract":"Accumulating evidences have indicated that disturbances in intracellular free calcium ([Ca2+]i) concentration play an important role in the pathophysiology of peripheral pain. Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. At least, 11 TRP channels in mammalian cells have been identified as thermosensitive TRP (thermo-TRP) channels (Uchida et al. 2017). Two TRP channels (TRPV1 and TRPV2) are activated by high temperatures. Five TRP channels (TRPV1-4 and TRPM2) are activated by different heat temperatures, although two of TRP channels (TRPA1 and TRPM8) are activated by cold and cool temperatures, respectively (Naziroglu and Braidy, 2017). It is well known that increase of [Ca2+]i concentration but decrease of intracellular Mg2+ levels induces activation of nitric oxide synthase (NOS) enzyme. By catalytic activity of NOS, nitric oxide synthetizes in neurons. In turn, it induces pain through production of excitatory amino acids and substance P (Medvedeva et al. 2008). Results of recent studies indicated involvement of chemothrepeutic agents (i.e. cisplatin, oxaliplatin and paclitaxel)-induced mitochondrial oxidative stress through activation of Thermo TRP channels such as TRPA1, TRPV1 and TRPM8, although antioxidants induced protective action on the pain induction through inhibition of the TRP channels in the experimental animals (Materazzi et al. 2012). In the oral presentation, I discussed novel effects of chemotherapeutic agents on the peripheral pain by the regulation of TRP channels. I concluded that the chemotherapeutic agents cause TRP channel activation and oxidative stress, which may lead to the pathology of peripheral pain. It seems to that the exact relationship between TRP channel activation and chemotherapeutic agents still remain to be determined.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44584648","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 the fourth most common neurological disorder and affects people of all ages. Medication for epilepsy is often life-long and has a major impact on the quality of life - mostly being related to substantial adverse effects. Therefore, over 30% of people with epilepsy do not achieve sufficient seizure control whilst effective medication being available. Ion channels are often primary targets of anticonvulsant drugs. They can either act as blockers for voltage gated sodium and calcium channels or as activators for potassium or chloride channels. Additionally, modulators of ligand gated ion channels (GABA or Glutamate receptors) are frequently used to treat epilepsy. Employing a panel of functional electrophysiological assays using fluorescence based methods and patch-clamping on a broad range of voltage and ligand gated ion channels, we were able to successfully screen for drugs with a beneficial action profile. In successful leads we found drugs that selectively interacted with TTX sensitive, neuronal voltage gated sodium channels. Activation and fast inactivation were unchanged, while an increased affinity in the slow inactivated state was observed. This profile is in contrast to traditional anticonvulsant drugs which show their major effects on the fast inactivated state of voltage gated sodium channels. One drug showed substantial shifts of the voltage dependence of the slow inactivation only for NaV1.2 and 1.6. This favours this drug for treating patients with diseases with compromised NaV1.1 function in interneurons, such as Alzheimer's disease.
{"title":"Voltage gated sodium channels and epilepsy","authors":"S. Hebeisen","doi":"10.37212/JCNOS.584668","DOIUrl":"https://doi.org/10.37212/JCNOS.584668","url":null,"abstract":"Epilepsy is the fourth most common neurological disorder and affects people of all ages. Medication for epilepsy is often life-long and has a major impact on the quality of life - mostly being related to substantial adverse effects. Therefore, over 30% of people with epilepsy do not achieve sufficient seizure control whilst effective medication being available. Ion channels are often primary targets of anticonvulsant drugs. They can either act as blockers for voltage gated sodium and calcium channels or as activators for potassium or chloride channels. Additionally, modulators of ligand gated ion channels (GABA or Glutamate receptors) are frequently used to treat epilepsy. Employing a panel of functional electrophysiological assays using fluorescence based methods and patch-clamping on a broad range of voltage and ligand gated ion channels, we were able to successfully screen for drugs with a beneficial action profile. In successful leads we found drugs that selectively interacted with TTX sensitive, neuronal voltage gated sodium channels. Activation and fast inactivation were unchanged, while an increased affinity in the slow inactivated state was observed. This profile is in contrast to traditional anticonvulsant drugs which show their major effects on the fast inactivated state of voltage gated sodium channels. One drug showed substantial shifts of the voltage dependence of the slow inactivation only for NaV1.2 and 1.6. This favours this drug for treating patients with diseases with compromised NaV1.1 function in interneurons, such as Alzheimer's disease.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43904538","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 one of the most frequent and heterogeneous neurological disorders and it is characterized by several disabilities. Epilepsy is affecting about 3% of people worldwide. Current antiepileptic drugs are only effective in 60% of individuals and many drugs can induce several unwanted side effects in patients. Etiology of epilepsy has not been clarified fully. However, increased intracellular calcium ion (Ca 2+ ) concentration has main role in etiology of epilepsy. Ca2+ passes the cell membrane through different cell membrane channels. One of the channels is TRP superfamily. The family is containing six subfamilies. TRPV1 channel is a member of TRPV subfamily. Capsaicin is a component of hot chili pepper. The TRPV1 channels is activated by different stimuli such as acidic pH, high temperature (≥ 42° C) and capsaicin, causing pain, inflammation and hyperalgesia in peripheral nervous system (Caterina et al. 1997). Is has been well known that hippocampus is main area in the brain for induction of epilepsy. Expression levels of TRPV1 channels in different areas of hippocampus are high (Gonzalez-Reyes et al. 2013). Results of recent studies indicated involvement of TRPV1 channels in epilepsy (Naziroglu and Ovey, 2015; Cho et al. 2018). In the oral presentation, I discussed novel roles of TRPV1 on the epilepsy induction by the capsaicin. Results of a recent study indicated increased levels of intracellular Ca2+ concentration in hippocampus of epilepsy induced rats (Naziroglu and Ovey, 2015). They also observed increased levels of intracellular mitochondrial oxidative stress and apoptosis levels in the neurons by the capsaicin stimulation. However, their levels were decreased by inhibition of TRPV1 channel blocker, capsazepine. I concluded that the results of recent studies suggest that TRPV1 stimulation through capsaicin causes oxidative stress and intracellular Ca2+ signaling in epileptic rats. It seems to that the certain role of TRPV1 channel activation in in the epilepsy still remains to be determined.
癫痫是最常见和异质性的神经系统疾病之一，其特点是几种残疾。全世界约有3%的人患有癫痫。目前的抗癫痫药物仅对60%的个体有效，而且许多药物会对患者产生一些不想要的副作用。癫痫的病因尚未完全清楚。然而，细胞内钙离子(ca2 +)浓度升高在癫痫发病中起主要作用。Ca2+通过不同的细胞膜通道通过细胞膜。其中一个通道是TRP超家族。这个科包含六个亚科。TRPV1通道是TRPV亚族的成员。辣椒素是辣椒的一种成分。TRPV1通道被酸性pH、高温(≥42℃)和辣椒素等不同刺激激活，引起周围神经系统疼痛、炎症和痛觉过敏(Caterina et al. 1997)。众所周知，海马体是大脑中诱发癫痫的主要区域。TRPV1通道在海马不同区域的表达水平较高(Gonzalez-Reyes et al. 2013)。最近的研究结果表明，TRPV1通道参与癫痫(Naziroglu和Ovey, 2015;Cho et al. 2018)。在口头报告中，我讨论了TRPV1在辣椒素诱导癫痫中的新作用。最近的一项研究结果表明，癫痫诱导大鼠海马细胞内Ca2+浓度水平升高(Naziroglu和Ovey, 2015)。他们还观察到，在辣椒素刺激下，神经元细胞内线粒体氧化应激水平和细胞凋亡水平增加。然而，它们的水平通过抑制TRPV1通道阻滞剂capsazepine而降低。我的结论是，最近的研究结果表明，通过辣椒素刺激TRPV1会引起癫痫大鼠的氧化应激和细胞内Ca2+信号传导。似乎TRPV1通道激活在癫痫中的作用仍有待确定。
{"title":"TRPV1 channel is a potential drug discovery channel for epilepsy","authors":"Ahmet Özşimşek","doi":"10.37212/JCNOS.610113","DOIUrl":"https://doi.org/10.37212/JCNOS.610113","url":null,"abstract":"Epilepsy is one of the most frequent and heterogeneous neurological disorders and it is characterized by several disabilities. Epilepsy is affecting about 3% of people worldwide. Current antiepileptic drugs are only effective in 60% of individuals and many drugs can induce several unwanted side effects in patients. Etiology of epilepsy has not been clarified fully. However, increased intracellular calcium ion (Ca 2+ ) concentration has main role in etiology of epilepsy. Ca2+ passes the cell membrane through different cell membrane channels. One of the channels is TRP superfamily. The family is containing six subfamilies. TRPV1 channel is a member of TRPV subfamily. Capsaicin is a component of hot chili pepper. The TRPV1 channels is activated by different stimuli such as acidic pH, high temperature (≥ 42° C) and capsaicin, causing pain, inflammation and hyperalgesia in peripheral nervous system (Caterina et al. 1997). Is has been well known that hippocampus is main area in the brain for induction of epilepsy. Expression levels of TRPV1 channels in different areas of hippocampus are high (Gonzalez-Reyes et al. 2013). Results of recent studies indicated involvement of TRPV1 channels in epilepsy (Naziroglu and Ovey, 2015; Cho et al. 2018). In the oral presentation, I discussed novel roles of TRPV1 on the epilepsy induction by the capsaicin. Results of a recent study indicated increased levels of intracellular Ca2+ concentration in hippocampus of epilepsy induced rats (Naziroglu and Ovey, 2015). They also observed increased levels of intracellular mitochondrial oxidative stress and apoptosis levels in the neurons by the capsaicin stimulation. However, their levels were decreased by inhibition of TRPV1 channel blocker, capsazepine. I concluded that the results of recent studies suggest that TRPV1 stimulation through capsaicin causes oxidative stress and intracellular Ca2+ signaling in epileptic rats. It seems to that the certain role of TRPV1 channel activation in in the epilepsy still remains to be determined.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47496251","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}
Oxidative stress in a neuron is induced by several physiological and pathological processes. Within the pathophysiological processes, ischemia-reperfusion injury has major role in the neurons and brain, because the neurons and brain are very sensitive to oxidative stress as compared to other tissues due to their high oxygen consumption rate and rich poly unsaturated fatty acid content but low antioxidant levels. Results of rodent studies indicated that exposure to volatile anesthetics as a result of ischemia-reperfusion injury can active leukocytes or alveolar macrophages, which, in turn, release inflammatory mediators and reactive oxygen species (ROS). This release of inflammatory mediators, ischemia/reperfusion injury, and ROS has been clearly demonstrated in generalized inflammatory reactions involving the production of phagocytic cells such as leucocytes and microglia. A common volatile general anesthetic is desflurane and results of several recent papers indicated that it an increase oxidative stress but can decrease antioxidant defense mechanisms through ischemia/reperfusion injury mechanisms. The excessive production of ROS is scavenged by enzymatic and non-enzymatic antioxidants. Major enzymatic antioxidants are vitamin A, vitamin C, vitamin E, glutathione, alpha lipoic acid and melatonin. Major non enzymatic antioxidants are glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Superoxide radical is converted to hydrogen peroxide by SOD enzyme and then the hydrogen peroxide is converted to water by CAT and GSH-Px enzymes. Results of papers indicated that the CAT, GSH-Px, SOD, vitamin A, vitamin E and vitamin C values were decreased in plasma and erythrocytes of human and animals by desflurane anesthesia, but oxidative stress levels were increased by desflurane anesthesia (Allaouchiche et al. 2001; Ceylan et al. 2011; Yalcin et al. 2013). In the oral presentation, I will summarize the results of recent papers on oxidative stress and antioxidants in human and rodents. In conclusion, it seems that desflurane anesthesia has oxidant effects through down-regulating the enzymatic and non-enzymatic antioxidants but upregulating of lipid peroxidation.
{"title":"Role of desflurane on oxidative stress in neuroscience","authors":"Mustafa Kütük","doi":"10.37212/jcnos.610129","DOIUrl":"https://doi.org/10.37212/jcnos.610129","url":null,"abstract":"Oxidative stress in a neuron is induced by several physiological and pathological processes. Within the pathophysiological processes, ischemia-reperfusion injury has major role in the neurons and brain, because the neurons and brain are very sensitive to oxidative stress as compared to other tissues due to their high oxygen consumption rate and rich poly unsaturated fatty acid content but low antioxidant levels. Results of rodent studies indicated that exposure to volatile anesthetics as a result of ischemia-reperfusion injury can active leukocytes or alveolar macrophages, which, in turn, release inflammatory mediators and reactive oxygen species (ROS). This release of inflammatory mediators, ischemia/reperfusion injury, and ROS has been clearly demonstrated in generalized inflammatory reactions involving the production of phagocytic cells such as leucocytes and microglia. A common volatile general anesthetic is desflurane and results of several recent papers indicated that it an increase oxidative stress but can decrease antioxidant defense mechanisms through ischemia/reperfusion injury mechanisms. The excessive production of ROS is scavenged by enzymatic and non-enzymatic antioxidants. Major enzymatic antioxidants are vitamin A, vitamin C, vitamin E, glutathione, alpha lipoic acid and melatonin. Major non enzymatic antioxidants are glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Superoxide radical is converted to hydrogen peroxide by SOD enzyme and then the hydrogen peroxide is converted to water by CAT and GSH-Px enzymes. Results of papers indicated that the CAT, GSH-Px, SOD, vitamin A, vitamin E and vitamin C values were decreased in plasma and erythrocytes of human and animals by desflurane anesthesia, but oxidative stress levels were increased by desflurane anesthesia (Allaouchiche et al. 2001; Ceylan et al. 2011; Yalcin et al. 2013). In the oral presentation, I will summarize the results of recent papers on oxidative stress and antioxidants in human and rodents. In conclusion, it seems that desflurane anesthesia has oxidant effects through down-regulating the enzymatic and non-enzymatic antioxidants but upregulating of lipid peroxidation.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43896770","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}
Fibromyalgia (FM) is a common chronic pain syndrome affecting up to 2% of the adult population. Several factors such as excessive oxidative stress and overload calcium ion (Ca2+) influx play main roles in the etiology of FM. Several pharmaceutical drugs such as antidepressants and voltage-gated calcium channel blockers are recommended for the treatment of FM; however, they fail to produce a satisfactory response in patients with FM because of the unclear etiology of the disease. Transient receptor potential (TRP) channels have six subfamilies and 27 members in human. Most of these channels are responsible in dorsal root ganglia (DRG) neurons for the Ca2+ permeation especially in neuronal cells. Expression level of the TRPM2 and TRPV1 channels are high in the DRG neurons and they show oxidative stress dependent activation (Tan and McNaughton 2016; Santos et al. 2018). The TRPM2 and TRPV1 channel expression levels in the DRG increased in different types of pain. Selenium as an antioxidant trace element is implicated as a neuroprotective agent in peripheral pain through the inhibition of apoptosis and regulation of the TRPM2 and TRPV1 channels (Kahya et al. 2017). Since a decade, a recent theory have argued that both supporting of intracellular antioxidant system and extracellular antioxidant administration may helpful in fibromyalgia for the inhibition of TRP channels mediated Ca2+ influx (Yuksel et al. 2017). In the oral presentation, I discussed novel effects of selenium on the treatment of irregular oxidative status and fibromyalgia by the regulation of TRPM2 and TRPV1 channels in rats. In conclusion, present literature information indicated that protective effects of selenium on TRPM2 and TRPV1 channels may novel approach to treat FM induced pain and mitochondrial oxidative stress. However, the subject should be clarified by further studies.
纤维肌痛(FM)是一种常见的慢性疼痛综合征，影响多达2%的成年人。过多的氧化应激和过多的钙离子(Ca2+)内流等因素在FM的病因中起主要作用。一些药物如抗抑郁药和电压门控钙通道阻滞剂被推荐用于治疗FM;然而，由于该病的病因不明，它们不能在FM患者中产生令人满意的反应。人类瞬时受体电位(TRP)通道有6个亚家族27个成员。这些通道大多在背根神经节(DRG)神经元中负责Ca2+的渗透，特别是在神经元细胞中。DRG神经元中TRPM2和TRPV1通道的表达水平较高，它们表现出氧化应激依赖性激活(Tan和McNaughton 2016;Santos et al. 2018)。DRG中TRPM2和TRPV1通道表达水平在不同类型疼痛中均升高。硒作为一种抗氧化微量元素，通过抑制细胞凋亡和调节TRPM2和TRPV1通道，作为外周性疼痛的神经保护剂(Kahya et al. 2017)。近十年来，最近的一项理论认为，细胞内抗氧化系统和细胞外抗氧化给药可能有助于纤维肌痛抑制TRP通道介导的Ca2+内流(Yuksel等，2017)。在口头报告中，我讨论了硒通过调节大鼠TRPM2和TRPV1通道来治疗不规则氧化状态和纤维肌痛的新作用。综上所述，目前的文献信息表明，硒对TRPM2和TRPV1通道的保护作用可能是治疗FM诱导的疼痛和线粒体氧化应激的新途径。然而，这个问题应该通过进一步的研究来澄清。
{"title":"Involvement of TRP channels on fibromyalgiainduced pain","authors":"A. Doğru","doi":"10.37212/JCNOS.610116","DOIUrl":"https://doi.org/10.37212/JCNOS.610116","url":null,"abstract":"Fibromyalgia (FM) is a common chronic pain syndrome affecting up to 2% of the adult population. Several factors such as excessive oxidative stress and overload calcium ion (Ca2+) influx play main roles in the etiology of FM. Several pharmaceutical drugs such as antidepressants and voltage-gated calcium channel blockers are recommended for the treatment of FM; however, they fail to produce a satisfactory response in patients with FM because of the unclear etiology of the disease. Transient receptor potential (TRP) channels have six subfamilies and 27 members in human. Most of these channels are responsible in dorsal root ganglia (DRG) neurons for the Ca2+ permeation especially in neuronal cells. Expression level of the TRPM2 and TRPV1 channels are high in the DRG neurons and they show oxidative stress dependent activation (Tan and McNaughton 2016; Santos et al. 2018). The TRPM2 and TRPV1 channel expression levels in the DRG increased in different types of pain. Selenium as an antioxidant trace element is implicated as a neuroprotective agent in peripheral pain through the inhibition of apoptosis and regulation of the TRPM2 and TRPV1 channels (Kahya et al. 2017). Since a decade, a recent theory have argued that both supporting of intracellular antioxidant system and extracellular antioxidant administration may helpful in fibromyalgia for the inhibition of TRP channels mediated Ca2+ influx (Yuksel et al. 2017). In the oral presentation, I discussed novel effects of selenium on the treatment of irregular oxidative status and fibromyalgia by the regulation of TRPM2 and TRPV1 channels in rats. In conclusion, present literature information indicated that protective effects of selenium on TRPM2 and TRPV1 channels may novel approach to treat FM induced pain and mitochondrial oxidative stress. However, the subject should be clarified by further studies.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42696323","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}
Mitochondria are providing an essential amount of energy to the cell, to achieve in homeostasis, metabolic increases, proliferation and differentiation processes. Also, mitochondrial deficiencies have severe or lethal impacts on cell viability. Among the 3000 proteins involved in mitochondrial activities, ATAD3 is a major one as essential for mitochondrial biogenesis, vital as early as embryonic implantation. In order to see its impact at animal level, we have used ATAD3+/- mice to investigate its role in running training and in high calorie diet. We found here that ATAD3 expression level avoids running capacity improvement and has a strong effect on weight increase, underlying its important role in mitochondrial mass regulations. Prior to this presentation we will emphasize on the potential of Western-blot, PCR and immunofluorescence analysis in biomedical researches.
{"title":"Western-blot, PCR and immunofluorescence analysis in mitochondrial biogenesis studies","authors":"D. Rousseau","doi":"10.37212/jcnos.609964","DOIUrl":"https://doi.org/10.37212/jcnos.609964","url":null,"abstract":"Mitochondria are providing an essential amount of energy to the cell, to achieve in homeostasis, metabolic increases, proliferation and differentiation processes. Also, mitochondrial deficiencies have severe or lethal impacts on cell viability. Among the 3000 proteins involved in mitochondrial activities, ATAD3 is a major one as essential for mitochondrial biogenesis, vital as early as embryonic implantation. In order to see its impact at animal level, we have used ATAD3+/- mice to investigate its role in running training and in high calorie diet. We found here that ATAD3 expression level avoids running capacity improvement and has a strong effect on weight increase, underlying its important role in mitochondrial mass regulations. Prior to this presentation we will emphasize on the potential of Western-blot, PCR and immunofluorescence analysis in biomedical researches.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47187816","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}
Parkinson's disease (PD) is a neurodegenerative disease that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. It is characterized by the relatively selective loss of dopaminergic neuronal cells in the substantia nigra pars compacta and the presence of alpha-synuclein aggregation named as Lewy bodies and Lewy neurites in surviving affected neurons. Nigrostriatal dopaminergic neurodegeneration is shared with other parkinsonian disorders, including some genetic forms of parkinsonism, but many of these disorders do not have Lewy bodies. An ideal animal model for PD, therefore, should exhibit age-dependent and progressive dopaminergic neurodegeneration, motor and non-motor dysfunction, and abnormal alpha-synuclein pathology. A wide range of neurotoxic agents are used to induce PD, alterations that are similar with dose observed in human PD. These agents are classified mainly by administration route and the species involved. The toxins that are mainly used in present 6- hydroxydopamine, 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine, rotenone, paraquat, reserpine, methamphetamine, 3-nitrotyrosine and isoquinoline derivatives (Tieu, 2011; McDowell and Chesselet, 2012; Bezard et al. 2013). In addition, viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration and genetic LRRK2 models (PARK8 gene mutation) has been used (Jiang and Dickson, 2018). In conclusion, these models are only approximations, each possibly holding a certain degree of relevance. Thus, researchers should select models whose characteristics are most suitable for addressing the experimental question.
帕金森病(PD)是一种发展缓慢的神经退行性疾病;然而，没有有效的早期诊断方法，也没有治愈方法。其特征是黑质致密部多巴胺能神经元细胞相对选择性丧失，存活的受病神经元中存在称为路易小体和路易神经突的α -突触核蛋白聚集。黑质纹状体多巴胺能神经退行性变与其他帕金森病相同，包括一些遗传形式的帕金森病，但许多这些疾病没有路易体。因此，理想的帕金森病动物模型应该表现出年龄依赖性和进行性多巴胺能神经变性、运动和非运动功能障碍以及α -突触核蛋白异常病理。广泛的神经毒性药物被用于诱导PD，其改变与在人类PD中观察到的剂量相似。这些药剂主要按给药途径和涉及的种类分类。目前主要用于6-羟多巴胺、1-甲基-4-苯基-1,2,3,6-四氢吡啶、鱼tenone、百草枯、利血平、甲基苯丙胺、3-硝基酪氨酸和异喹啉衍生物的毒素(Tieu, 2011;McDowell and Chesselet, 2012;Bezard et al. 2013)。此外，病毒介导的人α-突触核蛋白的表达，以及从PD患者的路易小体中接种致病性α-突触核蛋白物种，已被用于准确建模进行性自繁殖神经变性和遗传LRRK2模型(PARK8基因突变)(Jiang和Dickson, 2018)。总之，这些模型只是近似值，每个模型可能都有一定程度的相关性。因此，研究人员应该选择最适合解决实验问题的模型。
{"title":"Experimental Parkinson’s disease models","authors":"E. İpek","doi":"10.37212/jcnos.610154","DOIUrl":"https://doi.org/10.37212/jcnos.610154","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disease that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. It is characterized by the relatively selective loss of dopaminergic neuronal cells in the substantia nigra pars compacta and the presence of alpha-synuclein aggregation named as Lewy bodies and Lewy neurites in surviving affected neurons. Nigrostriatal dopaminergic neurodegeneration is shared with other parkinsonian disorders, including some genetic forms of parkinsonism, but many of these disorders do not have Lewy bodies. An ideal animal model for PD, therefore, should exhibit age-dependent and progressive dopaminergic neurodegeneration, motor and non-motor dysfunction, and abnormal alpha-synuclein pathology. A wide range of neurotoxic agents are used to induce PD, alterations that are similar with dose observed in human PD. These agents are classified mainly by administration route and the species involved. The toxins that are mainly used in present 6- hydroxydopamine, 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine, rotenone, paraquat, reserpine, methamphetamine, 3-nitrotyrosine and isoquinoline derivatives (Tieu, 2011; McDowell and Chesselet, 2012; Bezard et al. 2013). In addition, viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration and genetic LRRK2 models (PARK8 gene mutation) has been used (Jiang and Dickson, 2018). In conclusion, these models are only approximations, each possibly holding a certain degree of relevance. Thus, researchers should select models whose characteristics are most suitable for addressing the experimental question.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70024659","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}
In neurons such as dorsal root ganglion (DRG) and trigeminal ganglia, calcium (Ca2+) and sodium ion concentrations are higher in in outside than in cytosol, although potassium ion concentration was higher in inside of the neurons than outside of the neurons. Within the ions, it has been suggested that a dysregulation of Ca2+ homeostasis acts a key role in the pathogenesis of oxidative stress associated nerve damage. Ca2+ is a main intracellular messenger involved in several physiological functions of neurons such survival, death, synaptic plasticity and neurotransmitter release. It has specific role in induction of peripheral pain. Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. The TRP superfamily is containing 6 subfamilies with 28 members in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the voltage gated calcium channels. Some TRP channels such as TRP melastatin 2 (TRPM2), melastatin 7 (TRPM7) and TRP ankyrin 1 (TRPA1) are activated by oxidative stress. Expression levels of TRPA1, TRPM2 and TRPM7 are high in DRG, phagocytic cells and hippocampus, respectively. Therefore, TRPM2 is important channels in physiological activity of phagocytic cells such as neutrophil and monocytes (Heiner et al. 2006). TRPM7 and TRPA1 have main roles in cerebral ischemia and peripheral pain molecular pathways, respectively (Carrasco et al. 2018; Sun, 2017). Till today specific antagonists of most TRP channels have not been discovered yet and they have potential targets for discovering drugs in neuroscience. In pain etiology, Ca2+ is important and it has been demonstrated in some studies that the administration of an antagonist to Ca2+ channels induces a reduction in chemotherapeutic agents-induced neuropathic pain. In the presentation, I discussed novel results of Ca2+ on the peripheral pain by the regulation of TRP channels. I concluded that the results of recent studies suggest that increased cytosolic Ca2+ has through inhibition of TRP channels main role in etiology of peripheral pain. It seems to that the TRP channels are potential target for treatment of peripheral pain.
在背根神经节(DRG)和三叉神经节等神经元中，钙离子(Ca2+)和钠离子浓度在胞质外高于胞质外，而钾离子浓度在胞质内高于胞质外。在离子内，已经提出Ca2+稳态失调在氧化应激相关神经损伤的发病机制中起关键作用。Ca2+是一种主要的细胞内信使，参与神经元的生存、死亡、突触可塑性和神经递质释放等多种生理功能。它在外周疼痛的诱导中有特殊的作用。Ca2+通过不同的通道通过细胞膜，如化学通道和电压门控通道。除了众所周知的阳离子通道外，最近还发现了瞬时受体电位(TRP)家族通道。在哺乳动物中，TRP超家族包含6个亚家族，共有28个成员。TRP通道的激活和抑制机制与电压门控钙通道有很大不同。一些TRP通道如TRP美拉他汀2 (TRPM2)、美拉他汀7 (TRPM7)和TRP锚蛋白1 (TRPA1)被氧化应激激活。TRPA1、TRPM2和TRPM7分别在DRG、吞噬细胞和海马中高表达。因此，TRPM2是嗜中性粒细胞和单核细胞等吞噬细胞生理活动的重要通道(Heiner et al. 2006)。TRPM7和TRPA1分别在脑缺血和外周疼痛分子通路中起主要作用(Carrasco et al. 2018;太阳,2017)。迄今为止，大多数TRP通道的特异性拮抗剂尚未被发现，它们在神经科学领域具有潜在的药物开发靶点。在疼痛病因学中，Ca2+是重要的，并且在一些研究中已经证明，Ca2+通道拮抗剂的施用可以减少化疗药物引起的神经性疼痛。在报告中，我讨论了Ca2+通过调节TRP通道对外周疼痛的新结果。我的结论是，最近的研究结果表明，细胞质Ca2+的增加通过抑制TRP通道在周围性疼痛的病因学中起主要作用。TRP通道似乎是治疗外周性疼痛的潜在靶点。
{"title":"Pathophysiology of cation channels in pain: Focus on TRP Channels","authors":"M. Naziroğlu","doi":"10.37212/JCNOS.609840","DOIUrl":"https://doi.org/10.37212/JCNOS.609840","url":null,"abstract":"In neurons such as dorsal root ganglion (DRG) and trigeminal ganglia, calcium (Ca2+) and sodium ion concentrations are higher in in outside than in cytosol, although potassium ion concentration was higher in inside of the neurons than outside of the neurons. Within the ions, it has been suggested that a dysregulation of Ca2+ homeostasis acts a key role in the pathogenesis of oxidative stress associated nerve damage. Ca2+ is a main intracellular messenger involved in several physiological functions of neurons such survival, death, synaptic plasticity and neurotransmitter release. It has specific role in induction of peripheral pain. Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. The TRP superfamily is containing 6 subfamilies with 28 members in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the voltage gated calcium channels. Some TRP channels such as TRP melastatin 2 (TRPM2), melastatin 7 (TRPM7) and TRP ankyrin 1 (TRPA1) are activated by oxidative stress. Expression levels of TRPA1, TRPM2 and TRPM7 are high in DRG, phagocytic cells and hippocampus, respectively. Therefore, TRPM2 is important channels in physiological activity of phagocytic cells such as neutrophil and monocytes (Heiner et al. 2006). TRPM7 and TRPA1 have main roles in cerebral ischemia and peripheral pain molecular pathways, respectively (Carrasco et al. 2018; Sun, 2017). Till today specific antagonists of most TRP channels have not been discovered yet and they have potential targets for discovering drugs in neuroscience. In pain etiology, Ca2+ is important and it has been demonstrated in some studies that the administration of an antagonist to Ca2+ channels induces a reduction in chemotherapeutic agents-induced neuropathic pain. In the presentation, I discussed novel results of Ca2+ on the peripheral pain by the regulation of TRP channels. I concluded that the results of recent studies suggest that increased cytosolic Ca2+ has through inhibition of TRP channels main role in etiology of peripheral pain. It seems to that the TRP channels are potential target for treatment of peripheral pain.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42072456","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}
An accumulating body of evidence indicates that abnormalities of intracellular free calcium ([Ca2+]i) concentration is caused by excessive levels of reactive oxygen species (ROS) in rats with cerebral ischemia in play an important role in the pathophysiology of cerebral ischemia (Miyanohara et al. 2015; Belrose and Jackson, 2018). Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. The TRP superfamily is containing 7 subfamilies with 28 members in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the voltage gated calcium channels. For example, TRPM2 channel is activated by ADP-ribose and oxidative stress, but TRPV1 channel is activated several stimuli, including capsaicin and oxidative stress (Belrose and Jackson, 2018). Dexmedetomidine (DEX) is an important drug for long-term sedation in intensive care patients because it induces a rapid response and is easily controllable. There is some modulator role of DEX on the [Ca2+]i concentration in several neurons (Akpinar et al. 2016). Results of a recent study indicated that DEX induced modulator role on cerebral ischemia-induced ROS, TRPM2 and TRPV1 channel activation in hippocampus of rats. I concluded that the results of recent studies suggest that DEX treatment reduces cerebral ischemiainduced oxidative stress and intracellular Ca2+ signaling through inhibition of TRP channels. It seems to that the exact relationship between TRP channel activation and DEX in cerebral ischemia still remains to be determined.
{"title":"Roles of dexmedetomidine and calcium signaling in cerebral ischemia: Focus TRP channels","authors":"Hacı Ömer Osmanlioğlu","doi":"10.37212/jcnos.610107","DOIUrl":"https://doi.org/10.37212/jcnos.610107","url":null,"abstract":"An accumulating body of evidence indicates that abnormalities of intracellular free calcium ([Ca2+]i) concentration is caused by excessive levels of reactive oxygen species (ROS) in rats with cerebral ischemia in play an important role in the pathophysiology of cerebral ischemia (Miyanohara et al. 2015; Belrose and Jackson, 2018). Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. The TRP superfamily is containing 7 subfamilies with 28 members in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the voltage gated calcium channels. For example, TRPM2 channel is activated by ADP-ribose and oxidative stress, but TRPV1 channel is activated several stimuli, including capsaicin and oxidative stress (Belrose and Jackson, 2018). Dexmedetomidine (DEX) is an important drug for long-term sedation in intensive care patients because it induces a rapid response and is easily controllable. There is some modulator role of DEX on the [Ca2+]i concentration in several neurons (Akpinar et al. 2016). Results of a recent study indicated that DEX induced modulator role on cerebral ischemia-induced ROS, TRPM2 and TRPV1 channel activation in hippocampus of rats. I concluded that the results of recent studies suggest that DEX treatment reduces cerebral ischemiainduced oxidative stress and intracellular Ca2+ signaling through inhibition of TRP channels. It seems to that the exact relationship between TRP channel activation and DEX in cerebral ischemia still remains to be determined.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44872714","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}
Depression is a mental disorder that is estimated by the World Health Organization to affect 350 million people worldwide. But its pathogenesis and underlying mechanisms have not been understood yet. To present a satisfying explanation for the causes and treatments of these sorts of diseases animal models can be a powerful model for the researchers. Experimental animal research has been frequently used, in related with clinical studies, to test a number of hypotheses regarding the etiology of depression and its related behaviors. In the literature, experimental animal models about depression were described. These are chronic mild stress, forced swimming test, learned helplessness, tail suspension test, psycho-stimulant drug withdrawal and olfactory bulbectomy. In the oral presentation, it was summarized the experimental animal models that are used most commonly for depression, and discussed their advantages and limitations. In conclusion, it seems that some experimental animal models such as chronic mild stress and forced swimming test in several experiments have been using for investigating depression etiology and treatment and the models are very useful for searching the disease.
{"title":"Depression models in experimental animals","authors":"Arif Demirdaş","doi":"10.37212/JCNOS.610108","DOIUrl":"https://doi.org/10.37212/JCNOS.610108","url":null,"abstract":"Depression is a mental disorder that is estimated by the World Health Organization to affect 350 million people worldwide. But its pathogenesis and underlying mechanisms have not been understood yet. To present a satisfying explanation for the causes and treatments of these sorts of diseases animal models can be a powerful model for the researchers. Experimental animal research has been frequently used, in related with clinical studies, to test a number of hypotheses regarding the etiology of depression and its related behaviors. In the literature, experimental animal models about depression were described. These are chronic mild stress, forced swimming test, learned helplessness, tail suspension test, psycho-stimulant drug withdrawal and olfactory bulbectomy. In the oral presentation, it was summarized the experimental animal models that are used most commonly for depression, and discussed their advantages and limitations. In conclusion, it seems that some experimental animal models such as chronic mild stress and forced swimming test in several experiments have been using for investigating depression etiology and treatment and the models are very useful for searching the disease.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44062072","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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