The Experts below are selected from a list of 182217 Experts worldwide ranked by ideXlab platform
Hiroshi Okamoto - One of the best experts on this subject based on the ideXlab platform.
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Production and Characterization of Reg Knockout Mice: Reduced Proliferation of Pancreatic β-Cells in Reg Knockout Mice
Diabetes, 2002Co-Authors: Michiaki Unno, Koji Nata, Naoya Noguchi, Yoichi Narushima, Takako Akiyama, Takayuki Ikeda, Kei Nakagawa, Shin Takasawa, Hiroshi OkamotoAbstract:Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated in vitro and in vivo that the exogenous addition of rat and human Reg gene products, Reg/REG proteins, induced β-cell replication via the Reg receptor and thereby ameliorated experimental diabetes. In the present study, we produced Reg Knockout Mice by homologous recombination. The Reg gene disruption resulted in a null mutation. Knockout Mice developed normally. Islets from the Reg Knockout Mice appeared morphologically indistinguishable from those of normal controls. However, [3H]thymidine incorporation in isolated islets from Reg Knockout Mice was decreased. When hyperplastic islets were induced by the injection of goldthioglucose, the average islet size in Reg Knockout Mice was significantly smaller than that of control Reg+/+ Mice. We then produced transgenic Mice carrying the Reg gene under the control of the rat insulin II promoter (Ins-Reg) to express Reg in β-cells. Isolated islets from the Ins-Reg transgenic Mice showed increased [3H]thymidine incorporation. By intercrossing, we produced NOD Mice carrying the Ins-Reg transgene and found that development of diabetes in the resultant Ins-Reg transgenic NOD Mice was significantly retarded, coinciding with an increase in the pancreatic β-cell mass. These results indicate that Reg plays an important role in β-cell growth/regeneration.
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Production and characterization of Reg Knockout Mice: reduced proliferation of pancreatic beta-cells in Reg Knockout Mice.
Diabetes, 2002Co-Authors: Michiaki Unno, Koji Nata, Naoya Noguchi, Yoichi Narushima, Takako Akiyama, Takayuki Ikeda, Kei Nakagawa, Shin Takasawa, Hiroshi OkamotoAbstract:Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated in vitro and in vivo that the exogenous addition of rat and human Reg gene products, Reg/REG proteins, induced beta-cell replication via the Reg receptor and thereby ameliorated experimental diabetes. In the present study, we produced Reg Knockout Mice by homologous recombination. The Reg gene disruption resulted in a null mutation. Knockout Mice developed normally. Islets from the Reg Knockout Mice appeared morphologically indistinguishable from those of normal controls. However, [(3)H]thymidine incorporation in isolated islets from Reg Knockout Mice was decreased. When hyperplastic islets were induced by the injection of goldthioglucose, the average islet size in Reg Knockout Mice was significantly smaller than that of control Reg(+/+) Mice. We then produced transgenic Mice carrying the Reg gene under the control of the rat insulin II promoter (Ins-Reg) to express Reg in beta-cells. Isolated islets from the Ins-Reg transgenic Mice showed increased [(3)H]thymidine incorporation. By intercrossing, we produced NOD Mice carrying the Ins-Reg transgene and found that development of diabetes in the resultant Ins-Reg transgenic NOD Mice was significantly retarded, coinciding with an increase in the pancreatic beta-cell mass. These results indicate that Reg plays an important role in beta-cell growth/regeneration.
Toshitaka Nabeshima - One of the best experts on this subject based on the ideXlab platform.
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Morphine tolerance and dependence in the nociceptin receptor Knockout Mice.
Journal of neural transmission (Vienna Austria : 1996), 2001Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Xiuhai Ren, Taku Nagai, Makoto Ukai, Toshitaka NabeshimaAbstract:Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor Knockout Mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor Knockout Mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to Mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor Knockout Mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor Knockout Mice, the jumping signs in the nociceptin receptor Knockout Mice were less severe than those in wild-type Mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type Mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor Knockout Mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor Knockout Mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.
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Enhancement of spatial attention in nociceptin/orphanin FQ receptor-Knockout Mice
Brain research, 1998Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Miyuki Nishi, Toshitaka NabeshimaAbstract:We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-Knockout Mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-Knockout Mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in Mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-Knockout Mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type Mice. The nociceptin receptor-Knockout Mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-Knockout Mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type Mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-Knockout Mice than wild-type Mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
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enhancement of spatial attention in nociceptin orphanin fq receptor Knockout Mice
Brain Research, 1998Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Miyuki Nishi, Toshitaka NabeshimaAbstract:We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-Knockout Mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-Knockout Mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in Mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-Knockout Mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type Mice. The nociceptin receptor-Knockout Mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-Knockout Mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type Mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-Knockout Mice than wild-type Mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
Hiroshi Takeshima - One of the best experts on this subject based on the ideXlab platform.
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Enhanced hippocampal acetylcholine release in nociceptin-receptor Knockout Mice.
Brain research, 2005Co-Authors: Kayoko Uezu, Hiroshi Takeshima, Atsuko Sano, Hiroyoshi Sei, Kazunori Toida, Takeshi Houtani, Tetsuo Sugimoto, Toshiko Suzuki-yamamoto, Kazunori Ishimura, Yusuke MoritaAbstract:Nociceptin (NOC), an endogenous ligand of the opioid receptor-like 1 receptor, is thought to be involved in learning and memory processes. Since acetylcholine (ACh) is involved in hippocampal function, and the hippocampus plays a critical role on the learning and memory function, hippocampal ACh release in NOC-receptor Knockout Mice was examined using an in vivo microdialysis method. The release of hippocampal ACh was largely increased in the Knockout Mice. Furthermore, in the Knockout Mice, an enhanced hippocampal theta rhythm, which is known to be linked to hippocampal memory function, was also observed. Immunohistochemically, in septum, co-existence of NOC receptor with cholinergic, but not with GABAergic neurons, was verified. The findings demonstrate that the NOC receptor is involved in hippocampal cholinergic function.
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Methamphetamine sensitization in nociceptin receptor Knockout Mice: locomotor and c-fos expression.
European journal of pharmacology, 2004Co-Authors: Chinami Okabe, Hiroshi Takeshima, Niall P. MurphyAbstract:The role of endogenous nociceptin in the development and expression of sensitization to repeated methamphetamine administration in a novel environment was studied in nociceptin receptor Knockout Mice. No differences in acute or sensitized locomotor responses were found in nociceptin receptor Knockout Mice. However, analysis of c-fos expression revealed significant interactions between chronic methamphetamine treatment and genotype in the nucleus accumbens and lateral septum. This was due to increased c-fos expression in chronically methamphetamine-treated nociceptin receptor Knockout Mice contrasted with reduced c-fos expression in chronically vehicle-treated nociceptin receptor Knockout Mice. Two further regions (nucleus accumbens core and ventromedial caudate putamen) showed significant interactions between genotype, chronic, and acute methamphetamine treatment due to accentuated c-fos expression in nociceptin receptor Knockout Mice sensitized and challenged with methamphetamine. These findings suggest endogenous nociceptin modulates the response of the central nervous system to repeated psychostimulant administration, although this is little reflected in locomotion.
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Morphine tolerance and dependence in the nociceptin receptor Knockout Mice.
Journal of neural transmission (Vienna Austria : 1996), 2001Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Xiuhai Ren, Taku Nagai, Makoto Ukai, Toshitaka NabeshimaAbstract:Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor Knockout Mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor Knockout Mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to Mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor Knockout Mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor Knockout Mice, the jumping signs in the nociceptin receptor Knockout Mice were less severe than those in wild-type Mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type Mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor Knockout Mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor Knockout Mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.
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Enhancement of spatial attention in nociceptin/orphanin FQ receptor-Knockout Mice
Brain research, 1998Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Miyuki Nishi, Toshitaka NabeshimaAbstract:We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-Knockout Mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-Knockout Mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in Mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-Knockout Mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type Mice. The nociceptin receptor-Knockout Mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-Knockout Mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type Mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-Knockout Mice than wild-type Mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
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enhancement of spatial attention in nociceptin orphanin fq receptor Knockout Mice
Brain Research, 1998Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Miyuki Nishi, Toshitaka NabeshimaAbstract:We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-Knockout Mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-Knockout Mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in Mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-Knockout Mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type Mice. The nociceptin receptor-Knockout Mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-Knockout Mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type Mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-Knockout Mice than wild-type Mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
Michiaki Unno - One of the best experts on this subject based on the ideXlab platform.
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Production and Characterization of Reg Knockout Mice: Reduced Proliferation of Pancreatic β-Cells in Reg Knockout Mice
Diabetes, 2002Co-Authors: Michiaki Unno, Koji Nata, Naoya Noguchi, Yoichi Narushima, Takako Akiyama, Takayuki Ikeda, Kei Nakagawa, Shin Takasawa, Hiroshi OkamotoAbstract:Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated in vitro and in vivo that the exogenous addition of rat and human Reg gene products, Reg/REG proteins, induced β-cell replication via the Reg receptor and thereby ameliorated experimental diabetes. In the present study, we produced Reg Knockout Mice by homologous recombination. The Reg gene disruption resulted in a null mutation. Knockout Mice developed normally. Islets from the Reg Knockout Mice appeared morphologically indistinguishable from those of normal controls. However, [3H]thymidine incorporation in isolated islets from Reg Knockout Mice was decreased. When hyperplastic islets were induced by the injection of goldthioglucose, the average islet size in Reg Knockout Mice was significantly smaller than that of control Reg+/+ Mice. We then produced transgenic Mice carrying the Reg gene under the control of the rat insulin II promoter (Ins-Reg) to express Reg in β-cells. Isolated islets from the Ins-Reg transgenic Mice showed increased [3H]thymidine incorporation. By intercrossing, we produced NOD Mice carrying the Ins-Reg transgene and found that development of diabetes in the resultant Ins-Reg transgenic NOD Mice was significantly retarded, coinciding with an increase in the pancreatic β-cell mass. These results indicate that Reg plays an important role in β-cell growth/regeneration.
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Production and characterization of Reg Knockout Mice: reduced proliferation of pancreatic beta-cells in Reg Knockout Mice.
Diabetes, 2002Co-Authors: Michiaki Unno, Koji Nata, Naoya Noguchi, Yoichi Narushima, Takako Akiyama, Takayuki Ikeda, Kei Nakagawa, Shin Takasawa, Hiroshi OkamotoAbstract:Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated in vitro and in vivo that the exogenous addition of rat and human Reg gene products, Reg/REG proteins, induced beta-cell replication via the Reg receptor and thereby ameliorated experimental diabetes. In the present study, we produced Reg Knockout Mice by homologous recombination. The Reg gene disruption resulted in a null mutation. Knockout Mice developed normally. Islets from the Reg Knockout Mice appeared morphologically indistinguishable from those of normal controls. However, [(3)H]thymidine incorporation in isolated islets from Reg Knockout Mice was decreased. When hyperplastic islets were induced by the injection of goldthioglucose, the average islet size in Reg Knockout Mice was significantly smaller than that of control Reg(+/+) Mice. We then produced transgenic Mice carrying the Reg gene under the control of the rat insulin II promoter (Ins-Reg) to express Reg in beta-cells. Isolated islets from the Ins-Reg transgenic Mice showed increased [(3)H]thymidine incorporation. By intercrossing, we produced NOD Mice carrying the Ins-Reg transgene and found that development of diabetes in the resultant Ins-Reg transgenic NOD Mice was significantly retarded, coinciding with an increase in the pancreatic beta-cell mass. These results indicate that Reg plays an important role in beta-cell growth/regeneration.
Takayoshi Mamiya - One of the best experts on this subject based on the ideXlab platform.
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Morphine tolerance and dependence in the nociceptin receptor Knockout Mice.
Journal of neural transmission (Vienna Austria : 1996), 2001Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Xiuhai Ren, Taku Nagai, Makoto Ukai, Toshitaka NabeshimaAbstract:Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor Knockout Mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor Knockout Mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to Mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor Knockout Mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor Knockout Mice, the jumping signs in the nociceptin receptor Knockout Mice were less severe than those in wild-type Mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type Mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor Knockout Mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor Knockout Mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.
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Enhancement of spatial attention in nociceptin/orphanin FQ receptor-Knockout Mice
Brain research, 1998Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Miyuki Nishi, Toshitaka NabeshimaAbstract:We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-Knockout Mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-Knockout Mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in Mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-Knockout Mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type Mice. The nociceptin receptor-Knockout Mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-Knockout Mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type Mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-Knockout Mice than wild-type Mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
-
enhancement of spatial attention in nociceptin orphanin fq receptor Knockout Mice
Brain Research, 1998Co-Authors: Takayoshi Mamiya, Hiroshi Takeshima, Yukihiro Noda, Miyuki Nishi, Toshitaka NabeshimaAbstract:We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-Knockout Mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-Knockout Mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in Mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-Knockout Mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type Mice. The nociceptin receptor-Knockout Mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-Knockout Mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type Mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-Knockout Mice than wild-type Mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
