Pub Date : 2008-12-31DOI: 10.2174/1874082000802010059
N. Adachi, H. Kunugi
Recent studies have elucidated mechanisms of brain-derived neurotrophic factor (BDNF) secretion, and impaired secretion of BDNF may be involved in the pathogenesis of several neuropsychiatric diseases. The huntingtin gene, for example, has been shown to regulate vesicular transport of BDNF, which may play a role in the neurodegeneration present in Huntington's disease. In animal studies, mice lacking calcium-dependent activator protein for secretion 2 (CADPS2), which is involved in the activity-dependent release of BDNF, showed several phenotypes including autistic behavior. A single nucleotide polymorphism that results in an amino-acid change (Val66Met) in the BDNF gene has been shown to cause a decline in the function of BDNF vesicular sorting and has been reported to be associated with behavioral and intermediate phenotypes (e.g., episodic memory) in humans. In this review, we introduce recent progress in the molecular mechanisms of BDNF secretion and discuss its possible role in the pathophysiology and treatment of neuropsy-
{"title":"Impaired Secretion of Brain-Derived Neurotrophic Factor and Neuropsychiatric Diseases","authors":"N. Adachi, H. Kunugi","doi":"10.2174/1874082000802010059","DOIUrl":"https://doi.org/10.2174/1874082000802010059","url":null,"abstract":"Recent studies have elucidated mechanisms of brain-derived neurotrophic factor (BDNF) secretion, and impaired secretion of BDNF may be involved in the pathogenesis of several neuropsychiatric diseases. The huntingtin gene, for example, has been shown to regulate vesicular transport of BDNF, which may play a role in the neurodegeneration present in Huntington's disease. In animal studies, mice lacking calcium-dependent activator protein for secretion 2 (CADPS2), which is involved in the activity-dependent release of BDNF, showed several phenotypes including autistic behavior. A single nucleotide polymorphism that results in an amino-acid change (Val66Met) in the BDNF gene has been shown to cause a decline in the function of BDNF vesicular sorting and has been reported to be associated with behavioral and intermediate phenotypes (e.g., episodic memory) in humans. In this review, we introduce recent progress in the molecular mechanisms of BDNF secretion and discuss its possible role in the pathophysiology and treatment of neuropsy-","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"1 1","pages":"59-64"},"PeriodicalIF":0.0,"publicationDate":"2008-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89795340","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}
Pub Date : 2008-12-16DOI: 10.2174/1874082000802010041
F. Lechin, B. Dijs
{"title":"Central Nervous System Circuitries Underlying Two Types of Peripheral Autonomic Nervous System Disorders~!2008-04-24~!2008-09-26~!2008-12-05~!","authors":"F. Lechin, B. Dijs","doi":"10.2174/1874082000802010041","DOIUrl":"https://doi.org/10.2174/1874082000802010041","url":null,"abstract":"","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"47 1","pages":"41-50"},"PeriodicalIF":0.0,"publicationDate":"2008-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78977901","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}
Pub Date : 2008-12-05DOI: 10.2174/1874082000802010051
Aleksander Talgøy Holten, C. Morland, K. Nordengen, V. Gundersen
Glutamate is established as the most important excitatory transmitter in the brain. The transmitter status of as- partate is debated. There is evidence that aspartate is released from nerve terminals by exocytosis. However, release through excitatory amino acid transporters (EAATs) could be an alternative mechanism. We further investigated this by use of light and quantitative electron microscopic immunocytochemistry. The nerve terminal localisation of aspartate was compared to that of glutamate using antibodies specifically recognising the amino acids. Rat hippocampal slices were in- cubated under normal (3 mM) and depolarising (55 mM) concentrations of K + with and without the excitatory amino acid transporter inhibitor threo-beta-benzyloxyaspartate (TBOA). If aspartate is released either through reversal of the EAATs or through exchange with synaptically released glutamate, we would expect that TBOA would block the depolarisation induced release of aspartate. We found, however, that there was a substantial depletion of aspartate, as well as of gluta- mate, from hippocampal nerve terminals during K + induced depolarisation in the presence of TBOA. The possibility that aspartate is released through exocytosis from synaptic vesicles was further investigated by the use of a D-aspartate uptake assay, including exposure of the slices to exogenous D-aspartate and the use of D-aspartate immunogold cytochemistry to localise D-aspartate in the fixed tissue. We found that D-aspartate taken up into the terminals was concentrated in synaptic vesicles as opposed to in the cytoplasmic matrix. This is in line with the presence in synaptic vesicles of the recently iden- tified vesicular transporter for aspartate.
{"title":"Vesicular Release of L- and D-Aspartate from Hippocampal Nerve Terminals: Immunogold Evidence","authors":"Aleksander Talgøy Holten, C. Morland, K. Nordengen, V. Gundersen","doi":"10.2174/1874082000802010051","DOIUrl":"https://doi.org/10.2174/1874082000802010051","url":null,"abstract":"Glutamate is established as the most important excitatory transmitter in the brain. The transmitter status of as- partate is debated. There is evidence that aspartate is released from nerve terminals by exocytosis. However, release through excitatory amino acid transporters (EAATs) could be an alternative mechanism. We further investigated this by use of light and quantitative electron microscopic immunocytochemistry. The nerve terminal localisation of aspartate was compared to that of glutamate using antibodies specifically recognising the amino acids. Rat hippocampal slices were in- cubated under normal (3 mM) and depolarising (55 mM) concentrations of K + with and without the excitatory amino acid transporter inhibitor threo-beta-benzyloxyaspartate (TBOA). If aspartate is released either through reversal of the EAATs or through exchange with synaptically released glutamate, we would expect that TBOA would block the depolarisation induced release of aspartate. We found, however, that there was a substantial depletion of aspartate, as well as of gluta- mate, from hippocampal nerve terminals during K + induced depolarisation in the presence of TBOA. The possibility that aspartate is released through exocytosis from synaptic vesicles was further investigated by the use of a D-aspartate uptake assay, including exposure of the slices to exogenous D-aspartate and the use of D-aspartate immunogold cytochemistry to localise D-aspartate in the fixed tissue. We found that D-aspartate taken up into the terminals was concentrated in synaptic vesicles as opposed to in the cytoplasmic matrix. This is in line with the presence in synaptic vesicles of the recently iden- tified vesicular transporter for aspartate.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89839855","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}
Pub Date : 2008-12-05DOI: 10.2174/1874082000802010036
Z. Castaño, R. Kypta
The use of "Housekeeping proteins" as loading controls in western blots requires that they do not change their level of expression. However, deviations from this rule have been observed. This study investigated the expression of the commonly used proteins HSP60, -tubulin, -actin and GAPDH by western blot during retinoic acid-induced differentia- tion of the embryonal carcinoma NTera-2 and the neuroblastoma SH-SY5Y cell lines. -actin was found to be a poor loading control, increasing significantly during differentiation, whereas HSP60 and GAPDH were the more evenly ex- pressed of those analysed. Our results underline the importance of selecting accurate loading controls in this biological context.
{"title":"Housekeeping Proteins: Limitations as References During Neuronal Differentiation","authors":"Z. Castaño, R. Kypta","doi":"10.2174/1874082000802010036","DOIUrl":"https://doi.org/10.2174/1874082000802010036","url":null,"abstract":"The use of \"Housekeeping proteins\" as loading controls in western blots requires that they do not change their level of expression. However, deviations from this rule have been observed. This study investigated the expression of the commonly used proteins HSP60, -tubulin, -actin and GAPDH by western blot during retinoic acid-induced differentia- tion of the embryonal carcinoma NTera-2 and the neuroblastoma SH-SY5Y cell lines. -actin was found to be a poor loading control, increasing significantly during differentiation, whereas HSP60 and GAPDH were the more evenly ex- pressed of those analysed. Our results underline the importance of selecting accurate loading controls in this biological context.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"37 1","pages":"36-40"},"PeriodicalIF":0.0,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89573043","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}
Pub Date : 2008-09-12DOI: 10.2174/1874082000802010024
Mohati Desai-Shah, K. Viele, G. Sparks, J. Nadolski, B. Hayden, V. Srinivasan, R. Cooper
An enhanced buildup of (Ca 2+ )i occurs during short-term facilitation (STF) at the crayfish neuromuscular junc- tion (NMJ). As a model system, this NMJ allows discrete postsynaptic quantal events to be counted and characterized in relation to STF. Providing 10 pulses, at 20 and 40Hz, we monitored postsynaptic quantal events over a discrete region of a nerve terminal with a focal macropatch electrode. Characteristics of quantal events were clustered into groups by peak amplitude and time to the peak amplitude. Since the synapses at this NMJ have varied spacing of active zones, number of active zones and synaptic size, the graded nature of synaptic recruitment is likely one means of titrating synaptic efficacy for the graded depolarization on the non-spiking muscle fiber. Synapses in this preparation would appear to have a "quan- tal signature" that can be used for quantifying their activity which is useful in estimating the overall number of active sites. We use mixture modeling to estimate n (number of active sites) and p (probability of vesicle fusion) from the quan- tal characteristics. In a preparation that was stimulated at 40Hz, synapses were recruited (increase in n) and the number active synapses increased in p. In a different preparation, p increased as the stimulation was changed from 20 to 40Hz, but n did not show a substantial increase; however, during the STF train, p increases slightly. This study provides a novel ap- proach in determining subsets of the single evoked quanta to better estimate n and p which describe synaptic function.
{"title":"Assessment of Synaptic Function During Short-Term Facilitation in Motor Nerve Terminals in the Crayfish","authors":"Mohati Desai-Shah, K. Viele, G. Sparks, J. Nadolski, B. Hayden, V. Srinivasan, R. Cooper","doi":"10.2174/1874082000802010024","DOIUrl":"https://doi.org/10.2174/1874082000802010024","url":null,"abstract":"An enhanced buildup of (Ca 2+ )i occurs during short-term facilitation (STF) at the crayfish neuromuscular junc- tion (NMJ). As a model system, this NMJ allows discrete postsynaptic quantal events to be counted and characterized in relation to STF. Providing 10 pulses, at 20 and 40Hz, we monitored postsynaptic quantal events over a discrete region of a nerve terminal with a focal macropatch electrode. Characteristics of quantal events were clustered into groups by peak amplitude and time to the peak amplitude. Since the synapses at this NMJ have varied spacing of active zones, number of active zones and synaptic size, the graded nature of synaptic recruitment is likely one means of titrating synaptic efficacy for the graded depolarization on the non-spiking muscle fiber. Synapses in this preparation would appear to have a \"quan- tal signature\" that can be used for quantifying their activity which is useful in estimating the overall number of active sites. We use mixture modeling to estimate n (number of active sites) and p (probability of vesicle fusion) from the quan- tal characteristics. In a preparation that was stimulated at 40Hz, synapses were recruited (increase in n) and the number active synapses increased in p. In a different preparation, p increased as the stimulation was changed from 20 to 40Hz, but n did not show a substantial increase; however, during the STF train, p increases slightly. This study provides a novel ap- proach in determining subsets of the single evoked quanta to better estimate n and p which describe synaptic function.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"19 1","pages":"24-35"},"PeriodicalIF":0.0,"publicationDate":"2008-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77720967","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}
Pub Date : 2008-07-14DOI: 10.2174/1874082000802010016
A. Johnstone, S. Kellie, R. Cooper
Synaptic depression that is induced by electrical stimulation of the glutamatergic neuromuscular junction (NMJ) of the crayfish can be offset by recruitment of vesicles from a presynaptic reserve pool. This recruitment occurs following treatment of the NMJ with serotonin (5-HT), which results in a delay in the onset of synaptic depression in- duced by high frequency stimulation. The results of this study demonstrate that the releasable vesicles are insufficiently replenished during high frequency stimulation and that the readily releasable pool of vesicles (RRP) can be enhanced by the reserve pool (RP) in the presence of 5-HT. Anatomical visualization of vesicular pools by transmission electron mi- croscopy after depression or during 5-HT treatment showed no differences in the number of docked and RRP vesicles. We propose that the RRP vesicles can recycle empty and that a role for 5-HT might be to induce a rapid enhancement of syn- aptic transmission during synaptic fatigue.
{"title":"Presynaptic Depression in Phasic Motor Nerve Terminals and Influence of 5-HT on Vesicle Dynamics","authors":"A. Johnstone, S. Kellie, R. Cooper","doi":"10.2174/1874082000802010016","DOIUrl":"https://doi.org/10.2174/1874082000802010016","url":null,"abstract":"Synaptic depression that is induced by electrical stimulation of the glutamatergic neuromuscular junction (NMJ) of the crayfish can be offset by recruitment of vesicles from a presynaptic reserve pool. This recruitment occurs following treatment of the NMJ with serotonin (5-HT), which results in a delay in the onset of synaptic depression in- duced by high frequency stimulation. The results of this study demonstrate that the releasable vesicles are insufficiently replenished during high frequency stimulation and that the readily releasable pool of vesicles (RRP) can be enhanced by the reserve pool (RP) in the presence of 5-HT. Anatomical visualization of vesicular pools by transmission electron mi- croscopy after depression or during 5-HT treatment showed no differences in the number of docked and RRP vesicles. We propose that the RRP vesicles can recycle empty and that a role for 5-HT might be to induce a rapid enhancement of syn- aptic transmission during synaptic fatigue.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"41 1","pages":"16-23"},"PeriodicalIF":0.0,"publicationDate":"2008-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87168959","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}
Pub Date : 2008-05-21DOI: 10.2174/1874082000802010006
Austin G. Milton, M. A. Hamilton-Bruce, S. Koblar, J. Jannes
Stroke is a polygenic disorder. Previous genetic studies focused on candidate genes influencing pathogenic processes, with little emphasis on genes influencing vascular risk factors. Previous research linked the ClC-Kb T481S poly- morphism to blood pressure (BP). We therefore undertook an association study to determine the relevance of this poly- morphism to stroke, particularly lacunar stroke, given its strong correlation with hypertension. We genotyped DNA from 180 patients with acute ischaemic stroke (44 having lacunar stroke) and 298 age- and gender-matched controls using a se- quence-specific polymerase chain reaction method (SS-PCR). We found no association between the ClC-Kb T481S poly- morphism and ischaemic stroke (Odds Ratio (OR): 0.87, 95% Confidence Interval (CI): 0.57-1.33). Stratification for stroke subtype did not alter this finding. This polymorphism showed a borderline association with history of hypertension (p=0.06) but was not associated with systolic or diastolic BP (p>0.05). To our knowledge there are no other studies pub- lished on this polymorphism and stroke.
{"title":"The ClC-KbT481S chloride channel gene polymorphism, ischaemic stroke and hypertension","authors":"Austin G. Milton, M. A. Hamilton-Bruce, S. Koblar, J. Jannes","doi":"10.2174/1874082000802010006","DOIUrl":"https://doi.org/10.2174/1874082000802010006","url":null,"abstract":"Stroke is a polygenic disorder. Previous genetic studies focused on candidate genes influencing pathogenic processes, with little emphasis on genes influencing vascular risk factors. Previous research linked the ClC-Kb T481S poly- morphism to blood pressure (BP). We therefore undertook an association study to determine the relevance of this poly- morphism to stroke, particularly lacunar stroke, given its strong correlation with hypertension. We genotyped DNA from 180 patients with acute ischaemic stroke (44 having lacunar stroke) and 298 age- and gender-matched controls using a se- quence-specific polymerase chain reaction method (SS-PCR). We found no association between the ClC-Kb T481S poly- morphism and ischaemic stroke (Odds Ratio (OR): 0.87, 95% Confidence Interval (CI): 0.57-1.33). Stratification for stroke subtype did not alter this finding. This polymorphism showed a borderline association with history of hypertension (p=0.06) but was not associated with systolic or diastolic BP (p>0.05). To our knowledge there are no other studies pub- lished on this polymorphism and stroke.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"63 1","pages":"6-8"},"PeriodicalIF":0.0,"publicationDate":"2008-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86656221","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}
Pub Date : 2008-01-22DOI: 10.2174/1874082000802010001
A. Lavezzi, L. Matturri
AIMS - To define firstly in man the localization and the anatomical boundaries of the parafacial respiratory group in the brainstem. Thereafter, to determine whether this center, given its essential role in the respiratory rhythm- generating circuit, showed abnormalities in sudden unexplained perinatal and infant deaths, like other nuclei and/or struc- tures of the brainstem and cerebellum checking vital functions, that we have previously reported. METHODS - In 67 brains collected from 29 stillbirths, 9 newborns and 29 infants, died of both known and unknown cause, an in-depth histological examination of the autonomic nervous system was made, according to the protocol rou- tinely followed by the Institute of Pathology, University of Milan. In particular we analyzed the parafacial and facial nu- clei in serial sections of caudal pons. RESULTS - We firstly identified and defined the normal structure of the parafacial/facial complex in control cases. Be- sides we diagnosed the hypoplasia of these nuclei in 75% of sudden unexplained fetal deaths and never after birth. CONCLUSIONS - We formulate the hypothesis that the hypoplasia of the parafacial/facial complex is a specific marker of unexplained stillbirth, and that the normal development of this complex is essential for extra-uterine life.
{"title":"Hypoplasia of the Parafacial/Facial Complex: A Very Frequent Finding in Sudden Unexplained Fetal Death","authors":"A. Lavezzi, L. Matturri","doi":"10.2174/1874082000802010001","DOIUrl":"https://doi.org/10.2174/1874082000802010001","url":null,"abstract":"AIMS - To define firstly in man the localization and the anatomical boundaries of the parafacial respiratory group in the brainstem. Thereafter, to determine whether this center, given its essential role in the respiratory rhythm- generating circuit, showed abnormalities in sudden unexplained perinatal and infant deaths, like other nuclei and/or struc- tures of the brainstem and cerebellum checking vital functions, that we have previously reported. METHODS - In 67 brains collected from 29 stillbirths, 9 newborns and 29 infants, died of both known and unknown cause, an in-depth histological examination of the autonomic nervous system was made, according to the protocol rou- tinely followed by the Institute of Pathology, University of Milan. In particular we analyzed the parafacial and facial nu- clei in serial sections of caudal pons. RESULTS - We firstly identified and defined the normal structure of the parafacial/facial complex in control cases. Be- sides we diagnosed the hypoplasia of these nuclei in 75% of sudden unexplained fetal deaths and never after birth. CONCLUSIONS - We formulate the hypothesis that the hypoplasia of the parafacial/facial complex is a specific marker of unexplained stillbirth, and that the normal development of this complex is essential for extra-uterine life.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"27 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2008-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74064445","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}
Pub Date : 2008-01-01DOI: 10.2174/1874082000802010009
Yiqing Zheng, Mark Rayner, Ling Feng, Xiaohua Hu, Xin Zheng, Ellalane Bearth, Jizhen Lin
The survival of cochlear epithelial cells is of considerable importance, biologically. However, little is known about the growth factor(s) that are involved in the survival of cochlear sensory epithelial cells. In this study, we demonstrated that epidermal growth factor (EGF) plays a role in the survival of cochlear epithelial cells. Firstly, the presence of the EGF signaling pathway was demonstrated in the developing cochlear tissues of rats and a sensory epithelial cell line (OC1): -- epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase (MAPKK), I kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), and B cell lymphoma 2 (Bcl-2). Secondly, the addition of EGF to OC1 increased the promoter activity of NF-κB and cell viability but not cell cycle progression and cell number increase -- which suggests that EGF is for cellular survival rather than cell proliferation of OC1. Finally, pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) and inhibitor kappa B alpha (IκBα) mutant (IκBαM, a specific inhibitor of NF-κB) abrogated the EGF-induced NF-κB activity and cell survival. These data suggest that EGF plays a role in the survival of cochlear sensory epithelial cells through the EGFR/MAPKK/IκBα/NF-κB/Bcl-2 pathway.
耳蜗上皮细胞的存活具有重要的生物学意义。然而，对于参与耳蜗感觉上皮细胞存活的生长因子知之甚少。在这项研究中，我们证明了表皮生长因子(EGF)在耳蜗上皮细胞的存活中起作用。首先，在发育中的大鼠耳蜗组织和感觉上皮细胞系(OC1)中证实了EGF信号通路的存在:表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶(MAPKK)、IκBα (IκBα)、核因子κB (NF-κB)和B细胞淋巴瘤2 (Bcl-2)。其次，在OC1中加入EGF可提高NF-κB启动子活性和细胞活力，但不能提高细胞周期进程和细胞数量，这表明EGF对OC1的细胞存活而不是细胞增殖起作用。最后，吡咯烷二硫代氨基甲酸酯(PDTC，一种NF-κB抑制剂)和κBα (i -κB α)突变体(i - Bα m，一种NF-κB特异性抑制剂)消除了egf诱导的NF-κB活性和细胞存活。这些数据表明，EGF通过EGFR/MAPKK/ i -κB α/NF-κB/Bcl-2通路在耳蜗感觉上皮细胞的存活中发挥作用。
{"title":"EGF Mediates Survival of Rat Cochlear Sensory Cells via an NF-κB Dependent Mechanism In Vitro.","authors":"Yiqing Zheng, Mark Rayner, Ling Feng, Xiaohua Hu, Xin Zheng, Ellalane Bearth, Jizhen Lin","doi":"10.2174/1874082000802010009","DOIUrl":"https://doi.org/10.2174/1874082000802010009","url":null,"abstract":"<p><p>The survival of cochlear epithelial cells is of considerable importance, biologically. However, little is known about the growth factor(s) that are involved in the survival of cochlear sensory epithelial cells. In this study, we demonstrated that epidermal growth factor (EGF) plays a role in the survival of cochlear epithelial cells. Firstly, the presence of the EGF signaling pathway was demonstrated in the developing cochlear tissues of rats and a sensory epithelial cell line (OC1): -- epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase (MAPKK), I kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), and B cell lymphoma 2 (Bcl-2). Secondly, the addition of EGF to OC1 increased the promoter activity of NF-κB and cell viability but not cell cycle progression and cell number increase -- which suggests that EGF is for cellular survival rather than cell proliferation of OC1. Finally, pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) and inhibitor kappa B alpha (IκBα) mutant (IκBαM, a specific inhibitor of NF-κB) abrogated the EGF-induced NF-κB activity and cell survival. These data suggest that EGF plays a role in the survival of cochlear sensory epithelial cells through the EGFR/MAPKK/IκBα/NF-κB/Bcl-2 pathway.</p>","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"2 ","pages":"9-15"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777680/pdf/nihms156393.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28514093","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}
Pub Date : 2007-12-07DOI: 10.2174/1874082000701010025
N. Espinosa, C. Labra, C. Rivadulla, J. Mariño, J. Cudeiro
Here we confirm our earlier findings that showed 1Hz rTMS over the primary visual cortex of the anesthetized cat, known to cause inhibition of the cortex, induces an increase in power in the slow, delta band of the EEG. We also demonstrate that these inhibitory effects of 1Hz rTMS may be measured as changes of spatiotemporal receptive field pa- rameters at the single cell level. We extend these observations to show that higher frequency stimulation of the cortex at 15Hz has the opposite effect of decreasing delta activity, which was also accompanied by significant increases in theta, alpha and beta bands. This highly reproducible EEG change may be useful as a simple marker to predict inhibitory or ex- citatory rTMS effects known to be dependent upon stimulation frequency.
{"title":"Effects on EEG of Low (1Hz) and High (15Hz) Frequency Repetitive Transcranial Magnetic Stimulation of the Visual Cortex: A Study in the Anesthetized Cat","authors":"N. Espinosa, C. Labra, C. Rivadulla, J. Mariño, J. Cudeiro","doi":"10.2174/1874082000701010025","DOIUrl":"https://doi.org/10.2174/1874082000701010025","url":null,"abstract":"Here we confirm our earlier findings that showed 1Hz rTMS over the primary visual cortex of the anesthetized cat, known to cause inhibition of the cortex, induces an increase in power in the slow, delta band of the EEG. We also demonstrate that these inhibitory effects of 1Hz rTMS may be measured as changes of spatiotemporal receptive field pa- rameters at the single cell level. We extend these observations to show that higher frequency stimulation of the cortex at 15Hz has the opposite effect of decreasing delta activity, which was also accompanied by significant increases in theta, alpha and beta bands. This highly reproducible EEG change may be useful as a simple marker to predict inhibitory or ex- citatory rTMS effects known to be dependent upon stimulation frequency.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"700 1","pages":"25-30"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74759349","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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