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Shoei Furukawa - One of the best experts on this subject based on the ideXlab platform.
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4 Methylcatechol induced heme oxygenase 1 exerts a protective effect against oxidative stress in cultured neural stem progenitor cells via pi3 kinase akt pathway
Biomedical Research-tokyo, 2010Co-Authors: Yoshiko Furukawa, Tomomi Urano, Misato Minamimura, Mitsunari Nakajima, Satoshi Okuyama, Shoei FurukawaAbstract:4-Methylcatechol (4MC), a stimulator of the synthesis of neurotrophin family members in various cells, was able to up-regulate the expression of heme oxygenase (HO)-1, a redox-sensitive inducible stress protein, in neural stem/progenitor cells (NS/PCs). RT-PCR analysis showed that 4MC induced HO-1 mRNA expression in a dose- and a time-dependent manner. The increase in HO-1 mRNA was followed by an increase in HO-1 protein content, which was confirmed by ELISA and Western blotting analysis. When NS/PCs were pretreated with 4MC before exposure to hydrogen peroxide (H2O2), most of the cells were rescued from the H2O2-induced death. 4MC enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) and Akt in a time-dependent manner. Pretreatment of cultures with a selective inhibitor of PI3 kinase (PI3K)/Akt, but not with one of MAPK/ERK, inhibited both the 4MCinduced HO-1 expression and neuroprotective effect, demonstrating that PI3K/Akt signaling pathway played a significant role in 4MC-induced HO-1 induction and neuroprotection. Taken together, our results suggest that 4MC activates the expression of HO-1 through the PI3K/Akt signaling pathway and that the HO-1 protein inhibits the death of NS/PCs induced by oxidative stress.
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synthesis of water soluble polymeric prodrugs possessing 4 Methylcatechol derivatives by mechanochemical solid state copolymerization and nature of drug release
Chemical & Pharmaceutical Bulletin, 2002Co-Authors: Shinichi Kondo, Yasushi Sasai, Masayuki Kuzuya, Shoei FurukawaAbstract:In this study we synthesized the water-soluble polymeric prodrugs possessing a 4-Methylcatechol (4MC) derivative as a side chain by mechanochemical solid-state copolymerization. 1-Benzoyl-4-Methylcatechol (Bz4MC) was selected as a model compound of 4MC, and its methacryloyl derivative (1) was synthesized. 6-O-Methacryloyl-D-galactose (2) was also prepared as a water-soluble monomer. The mechanochemical solid-state copolymerization of 1 and 2 was carried out to obtain the water-soluble polymeric prodrug possessing the Bz4MC as a side chain. The mechanochemical copolymerization of 1 and 2 proceeded to completion, and the polymeric prodrug produced possessed a narrow molecular weight distribution. Three kinds of polymeric prodrugs, whose compositions were different from one another, were hydrolyzed in vitro. The hydrolysis of these polymeric prodrugs proceeded to completion. The rate constants of hydrolysis decreased with increasing the mole fraction of 1 in polymeric prodrug. It was suggested that the rate constant of hydrolysis could be controlled by the composition, the mole fraction of 1 in the polymeric prodrug.
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4 Methylcatechol stimulates phosphorylation of trk family neurotrophin receptors and map kinases in cultured rat cortical neurons
Journal of Neuroscience Research, 2002Co-Authors: Ayako Sometani, Atsumi Nitta, Yoshiko Furukawa, Hiroshi Nomoto, Shoei FurukawaAbstract:Effects of 4-methycatechol (4MC), a potent stimulator of nerve growth factor and brain-derived neurotrophic factor (BDNF) synthesis, on phosphorylation of cellular molecules in cultured rat cortical neurons were examined. 4MC stimulated tyrosine phosphorylation of various proteins of molecular weight from 10-300 kDa including Trks, which are high-affinity neurotrophin receptors. Moreover, 4MC enhanced the phosphorylation of serine 133 of mitogen-activated protein kinase (MAPK/ERK) in a dose-dependent manner. Pretreatment of cultures with PD98059, a selective inhibitor of MAPK kinase (MEK-1), inhibited 4MC-induced phosphorylation of ERKs, demonstrating MEK-1-mediated activation. Therefore, it seems that 4MC triggered the phosphorylation of Trks, resulting in the activation of the subsequent MAPK/ERK signal cascade, or perhaps the involvement of BDNF action as 4MC can stimulate neuronal BDNF synthesis. The phosphorylation of MAPK/ERK was unaffected, however, in the presence of cycloheximide, a protein synthesis inhibitor, and K252a, a selective inhibitor of Trks, suggesting that the effect of newly synthesized BDNF was negligible on this event, and that primary sites of 4MC actions are not limited only to Trks. These results suggest that 4MC primarily activates multiple signal transduction molecules such as tyrosine kinases, including Trks. A significant increase in the survival rate of cortical neurons in the presence of 10 or 100 nM 4MC supported this idea, because the concentrations were much lower than those for stimulation of BDNF synthesis. Our results strongly suggest that the neurotrophic actions of 4MC found so far are mediated predominantly by direct activation of some intracellular signals including MAPK/ERK rather than by neurotrophin synthesis.
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stimulation of neurotrophin synthesis by 4 Methylcatechol a promising approach for neuroprotection
Biomedical Reviews, 1999Co-Authors: Shoei Furukawa, Atsumi Nitta, Yoshiko FurukawaAbstract:Neurotrophins play a crucial role in the differentiation, maintenance, and survival of various types of peripheral and central neurons. However, the therapeutic use of neurotrophins is limited by their inability to cross the blood-brain barrier and their instability in the bloodstream. One of the promising approaches to utilize neurotrophic actions of these molecules in the therapy of neurodegenerative diseases is the stimulation of neurotrophin synthesis. Here we review the effects of 4-Methylcatechol, a nonadrenergic catechol compound, on the synthesis of the neurotrophins nerve growth factor and brain-derived neurotrophic factor in the peripheral and central nervous system. The neuroprotective potential of 4-Methylcatechol in animal models of neurodegenerative disorders is discussed, and other agents that enhance neurotrophin synthesis are also mentioned. Biomedical Reviews 1999; 10: 45-54.
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4 Methylcatechol increases brain derived neurotrophic factor content and mrna expression in cultured brain cells and in rat brain in vivo
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Atsumi Nitta, Yoshiko Furukawa, Hidefumi Fukumitsu, Ayako Sometani, Makoto Ohmiya, Hiroshi Nomoto, Megumi Ito, Hisanori Ito, Shoei FurukawaAbstract:Practical use of brain-derived neurotrophic factor (BDNF) as therapy is limited by two serious problems, i.e., its inability to cross the blood-brain barrier and its instability in the bloodstream. In the present study, we investigated the effects of 4-Methylcatechol (4-MC), which stimulates nerve growth factor synthesis and protects against peripheral neuropathies in rats, on BDNF content and mRNA expression in cultured brain cells and in vivo in the rat brain. 4-MC elevated BDNF content in culture media of both rat astrocytes and neurons with different dose-response relations. The increase in BDNF mRNA level was correlated with the increase in BDNF content, demonstrating that 4-MC can stimulate BDNF synthesis of both neurons and astrocytes. Then we examined the in vivo effects of 4-MC. First, we found that ventricularly administered 4-MC facilitated an increase in the BDNF content in the cerebral cortex and hippocampus in association with its diffusion into the brain parenchyma. Second, i.p. administration of 4-MC enhanced BDNF mRNA expression in the infant rat brain, in which the blood-brain has not yet fully been established. These results demonstrate that 4-MC, once delivered into the brain, can stimulate BDNF synthesis.
Yoshiko Furukawa - One of the best experts on this subject based on the ideXlab platform.
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4 Methylcatechol induced heme oxygenase 1 exerts a protective effect against oxidative stress in cultured neural stem progenitor cells via pi3 kinase akt pathway
Biomedical Research-tokyo, 2010Co-Authors: Yoshiko Furukawa, Tomomi Urano, Misato Minamimura, Mitsunari Nakajima, Satoshi Okuyama, Shoei FurukawaAbstract:4-Methylcatechol (4MC), a stimulator of the synthesis of neurotrophin family members in various cells, was able to up-regulate the expression of heme oxygenase (HO)-1, a redox-sensitive inducible stress protein, in neural stem/progenitor cells (NS/PCs). RT-PCR analysis showed that 4MC induced HO-1 mRNA expression in a dose- and a time-dependent manner. The increase in HO-1 mRNA was followed by an increase in HO-1 protein content, which was confirmed by ELISA and Western blotting analysis. When NS/PCs were pretreated with 4MC before exposure to hydrogen peroxide (H2O2), most of the cells were rescued from the H2O2-induced death. 4MC enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) and Akt in a time-dependent manner. Pretreatment of cultures with a selective inhibitor of PI3 kinase (PI3K)/Akt, but not with one of MAPK/ERK, inhibited both the 4MCinduced HO-1 expression and neuroprotective effect, demonstrating that PI3K/Akt signaling pathway played a significant role in 4MC-induced HO-1 induction and neuroprotection. Taken together, our results suggest that 4MC activates the expression of HO-1 through the PI3K/Akt signaling pathway and that the HO-1 protein inhibits the death of NS/PCs induced by oxidative stress.
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4 Methylcatechol stimulates phosphorylation of trk family neurotrophin receptors and map kinases in cultured rat cortical neurons
Journal of Neuroscience Research, 2002Co-Authors: Ayako Sometani, Atsumi Nitta, Yoshiko Furukawa, Hiroshi Nomoto, Shoei FurukawaAbstract:Effects of 4-methycatechol (4MC), a potent stimulator of nerve growth factor and brain-derived neurotrophic factor (BDNF) synthesis, on phosphorylation of cellular molecules in cultured rat cortical neurons were examined. 4MC stimulated tyrosine phosphorylation of various proteins of molecular weight from 10-300 kDa including Trks, which are high-affinity neurotrophin receptors. Moreover, 4MC enhanced the phosphorylation of serine 133 of mitogen-activated protein kinase (MAPK/ERK) in a dose-dependent manner. Pretreatment of cultures with PD98059, a selective inhibitor of MAPK kinase (MEK-1), inhibited 4MC-induced phosphorylation of ERKs, demonstrating MEK-1-mediated activation. Therefore, it seems that 4MC triggered the phosphorylation of Trks, resulting in the activation of the subsequent MAPK/ERK signal cascade, or perhaps the involvement of BDNF action as 4MC can stimulate neuronal BDNF synthesis. The phosphorylation of MAPK/ERK was unaffected, however, in the presence of cycloheximide, a protein synthesis inhibitor, and K252a, a selective inhibitor of Trks, suggesting that the effect of newly synthesized BDNF was negligible on this event, and that primary sites of 4MC actions are not limited only to Trks. These results suggest that 4MC primarily activates multiple signal transduction molecules such as tyrosine kinases, including Trks. A significant increase in the survival rate of cortical neurons in the presence of 10 or 100 nM 4MC supported this idea, because the concentrations were much lower than those for stimulation of BDNF synthesis. Our results strongly suggest that the neurotrophic actions of 4MC found so far are mediated predominantly by direct activation of some intracellular signals including MAPK/ERK rather than by neurotrophin synthesis.
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stimulation of neurotrophin synthesis by 4 Methylcatechol a promising approach for neuroprotection
Biomedical Reviews, 1999Co-Authors: Shoei Furukawa, Atsumi Nitta, Yoshiko FurukawaAbstract:Neurotrophins play a crucial role in the differentiation, maintenance, and survival of various types of peripheral and central neurons. However, the therapeutic use of neurotrophins is limited by their inability to cross the blood-brain barrier and their instability in the bloodstream. One of the promising approaches to utilize neurotrophic actions of these molecules in the therapy of neurodegenerative diseases is the stimulation of neurotrophin synthesis. Here we review the effects of 4-Methylcatechol, a nonadrenergic catechol compound, on the synthesis of the neurotrophins nerve growth factor and brain-derived neurotrophic factor in the peripheral and central nervous system. The neuroprotective potential of 4-Methylcatechol in animal models of neurodegenerative disorders is discussed, and other agents that enhance neurotrophin synthesis are also mentioned. Biomedical Reviews 1999; 10: 45-54.
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4 Methylcatechol increases brain derived neurotrophic factor content and mrna expression in cultured brain cells and in rat brain in vivo
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Atsumi Nitta, Yoshiko Furukawa, Hidefumi Fukumitsu, Ayako Sometani, Makoto Ohmiya, Hiroshi Nomoto, Megumi Ito, Hisanori Ito, Shoei FurukawaAbstract:Practical use of brain-derived neurotrophic factor (BDNF) as therapy is limited by two serious problems, i.e., its inability to cross the blood-brain barrier and its instability in the bloodstream. In the present study, we investigated the effects of 4-Methylcatechol (4-MC), which stimulates nerve growth factor synthesis and protects against peripheral neuropathies in rats, on BDNF content and mRNA expression in cultured brain cells and in vivo in the rat brain. 4-MC elevated BDNF content in culture media of both rat astrocytes and neurons with different dose-response relations. The increase in BDNF mRNA level was correlated with the increase in BDNF content, demonstrating that 4-MC can stimulate BDNF synthesis of both neurons and astrocytes. Then we examined the in vivo effects of 4-MC. First, we found that ventricularly administered 4-MC facilitated an increase in the BDNF content in the cerebral cortex and hippocampus in association with its diffusion into the brain parenchyma. Second, i.p. administration of 4-MC enhanced BDNF mRNA expression in the infant rat brain, in which the blood-brain has not yet fully been established. These results demonstrate that 4-MC, once delivered into the brain, can stimulate BDNF synthesis.
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induction of a physiologically active brain derived neurotrophic factor in the infant rat brain by peripheral administration of 4 Methylcatechol
Neuroscience Letters, 1999Co-Authors: Hidefumi Fukumitsu, Yoshiko Furukawa, Atsumi Nitta, Ayako Sometani, Makoto Ohmiya, Hiroshi Nomoto, Shoei FurukawaAbstract:Effects of 4-Methylcatechol (4MC), a known potent stimulator of nerve growth factor (NGF) synthesis, on expression of brain-derived neurotrophic factor (BDNF) mRNA and BDNF-like immunoreactivity (BDNF-LI) was investigated in infant rat brains. A single intraperitoneal administration of 4MC caused transient increases in the levels of BDNF mRNA and BDNF-LI in neurons of the cerebral cortex from 1 to 3 h and 3 to 12 h, respectively, after the injection. Repetitive injections of 4MC to newborn rats (12-h intervals for 10 days) caused a marked and dose-dependent elevation of the level of BDNF mRNA in the whole brain besides elevating the number of cells containing calbindin D-28 and enhancing its immunoreactive intensity in the pyriform cortex and hippocampus. These findings demonstrate that 4MC stimulates de novo synthesis of BDNF in the infant rat brain, resulting in acceleration of the developmental expression of calbindin D-28.
Shigeru Matsukura - One of the best experts on this subject based on the ideXlab platform.
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a catechol derivative 4 Methylcatechol accelerates the recovery from experimental acrylamide induced neuropathy
Journal of Pharmacology and Experimental Therapeutics, 1996Co-Authors: Kazuko Saita, Takekazu Ohi, Yasuko Hanaoka, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Shigeru MatsukuraAbstract:Acrylamide (ACR) monomer produces neuropathy of the dying-back type and 4-Methylcatechol (4-MC) is a potent stimulator of endogenous nerve growth factor synthesis. In the present study, we investigated the efficacy of 4-MC in promoting recovery from experimental ACR neuropathy in rats. Twenty-two Sprague-Dawley rats were made neuropathic by ACR injections. They showed hindlimb paralysis, increment of landing foot spread distance and a statistically significant reduction in motor nerve conduction velocity. After the ACR neuropathy had been established, 12 of the rats were administered 4-MC for 2 weeks, and the other 10 were injected with phosphate-buffered saline alone. 4-MC-administered ACR neuropathy rats showed improvement, i.e., a decrease in landing foot spread distance, increase in motor nerve conduction velocity and increase in nerve growth factor content in the sciatic nerves in comparison with the corresponding values for ACR neuropathy rats given phosphate-buffered saline alone. A decreased number of large myelinated fiber with a reciprocal increase in small myelinated fiber number also was seen in the ACR neuropathy rats; however, this change was ameliorated in part by the administration of 4-MC. Therefore, these findings suggest that 4-MC can accelerate the recovery process clinically, electrophysiologically, biochemically and neuropathologically.
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effects of 4 Methylcatechol a stimulator of endogenous nerve growth factor synthesis on experimental acrylamide induced neuropathy in rats
Neurotoxicology, 1995Co-Authors: Kazuhiko Saita, Takekazu Ohi, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Yasuo Hanaoka, Shigeru MatsukuraAbstract:Acrylamide monomer (ACR) causes central-peripheral distal axonopathy. We induced neuropathy in rats by means of ACR injection as an experimental model of the dying-back type of peripheral neuropathy to assess the potential efficacy of 4-Methylcatechol (4-MC), a potent stimulator of endogenous nerve growth factor (NGF) synthesis, as a therapeutic agent for the axonal nerve lesion. ACR-induced neuropathy in rats resulted in a dying- back type of axonal degeneration, and a statistically significant reduction in motor nerve conduction velocity (MNCV), and density of large myelinated fibers. We administered 4-MC and ACR together to rats intraperitoneally and found improved clinical signs, andsignificantly more NGF content in sciatic nerves, faster MNCV, and greater myelinated fiber density than in rats given ACR alone. These findings suggest that 4-MC can prevent the progression of ACR-induced neuropathy and decreased NGF levels may be involved in the pathogenesis of ACR neuropathy.
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the therapeutic effects of 4 Methylcatechol a stimulator of endogenous nerve growth factor synthesis on experimental diabetic neuropathy in rats
Journal of the Neurological Sciences, 1994Co-Authors: Yasuo Hanaoka, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Shigeru MatsukuraAbstract:We investigated therapeutic effects of 4-Methylcatechol (4-MC), a non-amine catechol compound, on streptozotocin (STZ)-induced diabetic neuropathy in rats. 4-MC is one of the potent stimulators of endogenous nerve growth factor (NGF) synthesis both in vitro and in vivo. Diabetic rats showed a statistically significant reduction in motor nerve conduction velocity (MNCV), mean myelinated axon diameter, and NGF content in the sciatic nerve during the experimental period of 8 weeks. The 4-MC treatment started 4 weeks after the STZ injection resulted in significantly greater NGF content, faster MNCV, and larger mean myelinated nerve fiber diameter and axon diameter than in untreated diabetic rats. These findings suggest that a decreased NGF level in the diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy and that 4-MC treatment could be useful for diabetic neuropathy.
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effect of 4 Methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats
Experimental Neurology, 1992Co-Authors: Yasuo Hanaoka, Takekazu Ohi, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Shigeru MatsukuraAbstract:This study examined the effects of 4-Methylcatechol (4-MC), a nonamine catechol compound, on the neuropathic process of streptozotocin (STZ)-induced diabetic rats. 4-MC is one of the potent stimulators of nerve growth factor (NGF) synthesis at the cellular level and in cultured sciatic nerve segments of rats. Diabetic rats showed a statistically significant fall in sciatic motor nerve conduction velocity (MNCV) and a significantly reduced NGF content in the sciatic nerve (38.5 ± 2.8% of control, P < 0.01) during the experimental period of 4 weeks. 4-MC treatment of the diabetic rats for 4 weeks starting from the STZ injection elevated the NGF content (140% of untreated diabetic rats, P < 0.05) and prevented the reduction in MNCV, but no effect on high blood glucose levels was seen. These findings suggest that decreased NGF levels in the sciatic nerve of the experimental diabetic rat may be involved in the development of the diabetic neuropathic process and that 4-MC, which can elevate endogenous NGF levels in vivo, may compensate for the inhibitory effect of STZ on the NGF level in progressive diabetic neuropathy.
Kyozo Hayashi - One of the best experts on this subject based on the ideXlab platform.
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a catechol derivative 4 Methylcatechol accelerates the recovery from experimental acrylamide induced neuropathy
Journal of Pharmacology and Experimental Therapeutics, 1996Co-Authors: Kazuko Saita, Takekazu Ohi, Yasuko Hanaoka, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Shigeru MatsukuraAbstract:Acrylamide (ACR) monomer produces neuropathy of the dying-back type and 4-Methylcatechol (4-MC) is a potent stimulator of endogenous nerve growth factor synthesis. In the present study, we investigated the efficacy of 4-MC in promoting recovery from experimental ACR neuropathy in rats. Twenty-two Sprague-Dawley rats were made neuropathic by ACR injections. They showed hindlimb paralysis, increment of landing foot spread distance and a statistically significant reduction in motor nerve conduction velocity. After the ACR neuropathy had been established, 12 of the rats were administered 4-MC for 2 weeks, and the other 10 were injected with phosphate-buffered saline alone. 4-MC-administered ACR neuropathy rats showed improvement, i.e., a decrease in landing foot spread distance, increase in motor nerve conduction velocity and increase in nerve growth factor content in the sciatic nerves in comparison with the corresponding values for ACR neuropathy rats given phosphate-buffered saline alone. A decreased number of large myelinated fiber with a reciprocal increase in small myelinated fiber number also was seen in the ACR neuropathy rats; however, this change was ameliorated in part by the administration of 4-MC. Therefore, these findings suggest that 4-MC can accelerate the recovery process clinically, electrophysiologically, biochemically and neuropathologically.
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effects of 4 Methylcatechol a stimulator of endogenous nerve growth factor synthesis on experimental acrylamide induced neuropathy in rats
Neurotoxicology, 1995Co-Authors: Kazuhiko Saita, Takekazu Ohi, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Yasuo Hanaoka, Shigeru MatsukuraAbstract:Acrylamide monomer (ACR) causes central-peripheral distal axonopathy. We induced neuropathy in rats by means of ACR injection as an experimental model of the dying-back type of peripheral neuropathy to assess the potential efficacy of 4-Methylcatechol (4-MC), a potent stimulator of endogenous nerve growth factor (NGF) synthesis, as a therapeutic agent for the axonal nerve lesion. ACR-induced neuropathy in rats resulted in a dying- back type of axonal degeneration, and a statistically significant reduction in motor nerve conduction velocity (MNCV), and density of large myelinated fibers. We administered 4-MC and ACR together to rats intraperitoneally and found improved clinical signs, andsignificantly more NGF content in sciatic nerves, faster MNCV, and greater myelinated fiber density than in rats given ACR alone. These findings suggest that 4-MC can prevent the progression of ACR-induced neuropathy and decreased NGF levels may be involved in the pathogenesis of ACR neuropathy.
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the therapeutic effects of 4 Methylcatechol a stimulator of endogenous nerve growth factor synthesis on experimental diabetic neuropathy in rats
Journal of the Neurological Sciences, 1994Co-Authors: Yasuo Hanaoka, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Shigeru MatsukuraAbstract:We investigated therapeutic effects of 4-Methylcatechol (4-MC), a non-amine catechol compound, on streptozotocin (STZ)-induced diabetic neuropathy in rats. 4-MC is one of the potent stimulators of endogenous nerve growth factor (NGF) synthesis both in vitro and in vivo. Diabetic rats showed a statistically significant reduction in motor nerve conduction velocity (MNCV), mean myelinated axon diameter, and NGF content in the sciatic nerve during the experimental period of 8 weeks. The 4-MC treatment started 4 weeks after the STZ injection resulted in significantly greater NGF content, faster MNCV, and larger mean myelinated nerve fiber diameter and axon diameter than in untreated diabetic rats. These findings suggest that a decreased NGF level in the diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy and that 4-MC treatment could be useful for diabetic neuropathy.
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effect of 4 Methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats
Experimental Neurology, 1992Co-Authors: Yasuo Hanaoka, Takekazu Ohi, Shoei Furukawa, Yoshiko Furukawa, Kyozo Hayashi, Shigeru MatsukuraAbstract:This study examined the effects of 4-Methylcatechol (4-MC), a nonamine catechol compound, on the neuropathic process of streptozotocin (STZ)-induced diabetic rats. 4-MC is one of the potent stimulators of nerve growth factor (NGF) synthesis at the cellular level and in cultured sciatic nerve segments of rats. Diabetic rats showed a statistically significant fall in sciatic motor nerve conduction velocity (MNCV) and a significantly reduced NGF content in the sciatic nerve (38.5 ± 2.8% of control, P < 0.01) during the experimental period of 4 weeks. 4-MC treatment of the diabetic rats for 4 weeks starting from the STZ injection elevated the NGF content (140% of untreated diabetic rats, P < 0.05) and prevented the reduction in MNCV, but no effect on high blood glucose levels was seen. These findings suggest that decreased NGF levels in the sciatic nerve of the experimental diabetic rat may be involved in the development of the diabetic neuropathic process and that 4-MC, which can elevate endogenous NGF levels in vivo, may compensate for the inhibitory effect of STZ on the NGF level in progressive diabetic neuropathy.
Sungtsang Hsieh - One of the best experts on this subject based on the ideXlab platform.
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effects of 4 Methylcatechol on skin reinnervation promotion of cutaneous nerve regeneration after crush injury
Journal of Neuropathology and Experimental Neurology, 2009Co-Authors: Yulin Hsieh, Wheimin Lin, Junehorng Lue, Mingfong Chang, Sungtsang HsiehAbstract:We assessed the effects of treatment with 4-Methylcatechol (4MC), a known inducer of nerve growth factor, on peripheral nerve regeneration by analyzing cutaneous and muscular reinnervation in mice after sciatic nerve crush injury. At 3 months postinjury, the skin innervation index was significantly higher in the 4MC group than the control group (p=0.0002); there was also increased unmyelinated fiber density (p=0.0042) and unmyelinated fibers/Remak bundle (p = 0.001) in sural nerves, indicating unmyelinated nerve fiber regeneration. These changes were accompanied by increases of transcripts for nerve growth factor (p = 0.0026) and glial cell line-derived neurotrophic factor (p=0.03) in the 4MC group. In contrast, muscle innervation indices were similar in both groups and were higher than the skin innervation index (p < 0.0001). The regeneration of myelinated nerve fibers, as assessed by fiber density, diameter and g ratio analyses in sural nerves, and amplitudes of muscle action potential in sciatic nerves, was similar in both groups. Taken together, these data suggest that 4MC specifically promoted the regeneration of unmyelinated nerve fibers and reinnervation of the skin by increasing the expression of nerve growth factor and glial cell line-derived neurotrophic factor.
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enhancement of cutaneous nerve regeneration by 4 Methylcatechol in resiniferatoxin induced neuropathy
Journal of Neuropathology and Experimental Neurology, 2008Co-Authors: Yulin Hsieh, Hao Chiang, Tojung Tseng, Sungtsang HsiehAbstract:To generate an experimental neuropathy model in which small-diameter sensory nerves are specifically affected and to test a potential treatment, adult mice were given a single injection (50 μg/kg, i.p.) of the capsaicin analog resiniferatoxin (RTX). On Day 7 after RTX treatment, there was a 53% reduction in unmyelinated nerve density in the medial plantar nerve (p = 0.0067) and a 66% reduction in epidermal nerve density of hind paw skin (p = 0.0004) compared with vehicle-treated controls. Substance P-immunoreactive dorsal root ganglion neurons were also markedly depleted (p = 0.0001). These effects were associated with the functional deficit of prolonged withdrawal latencies to heat stimuli (p = 0.0007) on a hot plate test. The potential therapeutic effects of 4-Methylcatechol (4MC) on this neuropathy were then tested by daily injections of 4MC (10 μg/kg, i.p.) from Days 7 to 35 after neuropathy induction. On Day 35, 4MC-treated mice had an increase in unmyelinated (p = 0.014) and epidermal nerve (p = 0.0013) densities and a reduction in thermal withdrawal latency (p = 0.0091) compared with RTX-only controls. These results indicate that 4MC promoted regeneration of unmyelinated nerves in experimental RTX-induced neuropathy and enhanced function.
