Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain
Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal b...
Ausführliche Beschreibung
Autor*in: |
Shen, Xiaofeng [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2014 |
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Anmerkung: |
© Maj Institute of Pharmacology, Polish Academy of Sciences 2014 |
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Übergeordnetes Werk: |
Enthalten in: Pharmacological reports - Heidelberg : Springer Nature, 1998, 66(2014), 1 vom: Jan., Seite 49-55 |
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Übergeordnetes Werk: |
volume:66 ; year:2014 ; number:1 ; month:01 ; pages:49-55 |
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DOI / URN: |
10.1016/j.pharep.2013.06.005 |
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Katalog-ID: |
SPR038892200 |
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245 | 1 | 0 | |a Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain |
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520 | |a Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. | ||
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650 | 4 | |a Menin |7 (dpeaa)DE-He213 | |
650 | 4 | |a Neurotransmitter |7 (dpeaa)DE-He213 | |
650 | 4 | |a Neuropathic pain |7 (dpeaa)DE-He213 | |
650 | 4 | |a Epigenetics |7 (dpeaa)DE-He213 | |
700 | 1 | |a Liu, Yusheng |4 aut | |
700 | 1 | |a Xu, Shiqin |4 aut | |
700 | 1 | |a Zhao, Qingsong |4 aut | |
700 | 1 | |a Wu, Haibo |4 aut | |
700 | 1 | |a Guo, Xirong |4 aut | |
700 | 1 | |a Shen, Rong |4 aut | |
700 | 1 | |a Wang, Fuzhou |4 aut | |
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10.1016/j.pharep.2013.06.005 doi (DE-627)SPR038892200 (SPR)j.pharep.2013.06.005-e DE-627 ger DE-627 rakwb eng Shen, Xiaofeng verfasserin aut Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. Spinal cord (dpeaa)DE-He213 Menin (dpeaa)DE-He213 Neurotransmitter (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Liu, Yusheng aut Xu, Shiqin aut Zhao, Qingsong aut Wu, Haibo aut Guo, Xirong aut Shen, Rong aut Wang, Fuzhou aut Enthalten in Pharmacological reports Heidelberg : Springer Nature, 1998 66(2014), 1 vom: Jan., Seite 49-55 (DE-627)375964215 (DE-600)2129019-2 2299-5684 nnns volume:66 year:2014 number:1 month:01 pages:49-55 https://dx.doi.org/10.1016/j.pharep.2013.06.005 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 66 2014 1 01 49-55 |
spelling |
10.1016/j.pharep.2013.06.005 doi (DE-627)SPR038892200 (SPR)j.pharep.2013.06.005-e DE-627 ger DE-627 rakwb eng Shen, Xiaofeng verfasserin aut Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. Spinal cord (dpeaa)DE-He213 Menin (dpeaa)DE-He213 Neurotransmitter (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Liu, Yusheng aut Xu, Shiqin aut Zhao, Qingsong aut Wu, Haibo aut Guo, Xirong aut Shen, Rong aut Wang, Fuzhou aut Enthalten in Pharmacological reports Heidelberg : Springer Nature, 1998 66(2014), 1 vom: Jan., Seite 49-55 (DE-627)375964215 (DE-600)2129019-2 2299-5684 nnns volume:66 year:2014 number:1 month:01 pages:49-55 https://dx.doi.org/10.1016/j.pharep.2013.06.005 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 66 2014 1 01 49-55 |
allfields_unstemmed |
10.1016/j.pharep.2013.06.005 doi (DE-627)SPR038892200 (SPR)j.pharep.2013.06.005-e DE-627 ger DE-627 rakwb eng Shen, Xiaofeng verfasserin aut Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. Spinal cord (dpeaa)DE-He213 Menin (dpeaa)DE-He213 Neurotransmitter (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Liu, Yusheng aut Xu, Shiqin aut Zhao, Qingsong aut Wu, Haibo aut Guo, Xirong aut Shen, Rong aut Wang, Fuzhou aut Enthalten in Pharmacological reports Heidelberg : Springer Nature, 1998 66(2014), 1 vom: Jan., Seite 49-55 (DE-627)375964215 (DE-600)2129019-2 2299-5684 nnns volume:66 year:2014 number:1 month:01 pages:49-55 https://dx.doi.org/10.1016/j.pharep.2013.06.005 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 66 2014 1 01 49-55 |
allfieldsGer |
10.1016/j.pharep.2013.06.005 doi (DE-627)SPR038892200 (SPR)j.pharep.2013.06.005-e DE-627 ger DE-627 rakwb eng Shen, Xiaofeng verfasserin aut Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. Spinal cord (dpeaa)DE-He213 Menin (dpeaa)DE-He213 Neurotransmitter (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Liu, Yusheng aut Xu, Shiqin aut Zhao, Qingsong aut Wu, Haibo aut Guo, Xirong aut Shen, Rong aut Wang, Fuzhou aut Enthalten in Pharmacological reports Heidelberg : Springer Nature, 1998 66(2014), 1 vom: Jan., Seite 49-55 (DE-627)375964215 (DE-600)2129019-2 2299-5684 nnns volume:66 year:2014 number:1 month:01 pages:49-55 https://dx.doi.org/10.1016/j.pharep.2013.06.005 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 66 2014 1 01 49-55 |
allfieldsSound |
10.1016/j.pharep.2013.06.005 doi (DE-627)SPR038892200 (SPR)j.pharep.2013.06.005-e DE-627 ger DE-627 rakwb eng Shen, Xiaofeng verfasserin aut Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. Spinal cord (dpeaa)DE-He213 Menin (dpeaa)DE-He213 Neurotransmitter (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Liu, Yusheng aut Xu, Shiqin aut Zhao, Qingsong aut Wu, Haibo aut Guo, Xirong aut Shen, Rong aut Wang, Fuzhou aut Enthalten in Pharmacological reports Heidelberg : Springer Nature, 1998 66(2014), 1 vom: Jan., Seite 49-55 (DE-627)375964215 (DE-600)2129019-2 2299-5684 nnns volume:66 year:2014 number:1 month:01 pages:49-55 https://dx.doi.org/10.1016/j.pharep.2013.06.005 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 66 2014 1 01 49-55 |
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Enthalten in Pharmacological reports 66(2014), 1 vom: Jan., Seite 49-55 volume:66 year:2014 number:1 month:01 pages:49-55 |
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Shen, Xiaofeng @@aut@@ Liu, Yusheng @@aut@@ Xu, Shiqin @@aut@@ Zhao, Qingsong @@aut@@ Wu, Haibo @@aut@@ Guo, Xirong @@aut@@ Shen, Rong @@aut@@ Wang, Fuzhou @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR038892200</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230520013334.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2014 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.pharep.2013.06.005</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR038892200</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)j.pharep.2013.06.005-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Shen, Xiaofeng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Maj Institute of Pharmacology, Polish Academy of Sciences 2014</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. 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Shen, Xiaofeng |
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Shen, Xiaofeng misc Spinal cord misc Menin misc Neurotransmitter misc Neuropathic pain misc Epigenetics Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain |
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Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain Spinal cord (dpeaa)DE-He213 Menin (dpeaa)DE-He213 Neurotransmitter (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 |
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Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain |
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menin regulates spinal glutamate-gaba balance through gad65 contributing to neuropathic pain |
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Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain |
abstract |
Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 |
abstractGer |
Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 |
abstract_unstemmed |
Background Our previous work found that tumor suppressor menin potentiates spinal synaptic plasticity in the context of peripheral nerve injury-induced neuropathic hypersensitivity, but the underlying molecular mechanisms are not clear. We hereby assessed the role of menin in regulating the spinal balance between glutamate and GABA and its contribution to the pathological condition of nerve injury-induced hypersensitivity. Methods In spared nerve injury induced C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey filaments after intrathecal administration of small interfering RNA (siRNA) of MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high-performance liquid chromatography were used to detect the level of protein expression and spinal glutamate and GABA, respectively. Results Genetic knockdown of spinal menin alleviated nerve injury evoked mechanical hypersensitivity, which was strongly associated with the alteration of the spinal level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the baseline ratio of 5.8 ± 0.9 (×$ 10^{−4} $) to the peak value of 58.6 ± 11.8 (×$ 10^{−4} $) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7 ± 2.1 (×$ 10^{−4} $) at the day 14 after nerve injury (p < 0.01). In further, selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate and GABA, and also alleviated the mechanical withdrawal threshold markedly. Conclusion Our findings provide mechanistic insight into the contribution of the upregulated spinal menin to peripheral nerve injury induced neuropathic hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65. © Maj Institute of Pharmacology, Polish Academy of Sciences 2014 |
collection_details |
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container_issue |
1 |
title_short |
Menin regulates spinal glutamate-GABA balance through GAD65 contributing to neuropathic pain |
url |
https://dx.doi.org/10.1016/j.pharep.2013.06.005 |
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Liu, Yusheng Xu, Shiqin Zhao, Qingsong Wu, Haibo Guo, Xirong Shen, Rong Wang, Fuzhou |
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Liu, Yusheng Xu, Shiqin Zhao, Qingsong Wu, Haibo Guo, Xirong Shen, Rong Wang, Fuzhou |
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doi_str |
10.1016/j.pharep.2013.06.005 |
up_date |
2024-07-03T20:34:07.879Z |
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score |
7.4017677 |