Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression
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摘要
Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages. To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation. Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation. We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor. Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. Sodium butyrate pretreatment reversed these changes. These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No. KIRAMS16-0002) on December 30, 2016.
Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages. To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation. Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation. We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor. Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. Sodium butyrate pretreatment reversed these changes. These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No. KIRAMS16-0002) on December 30, 2016.
Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages. To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation. Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation. We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor. Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. Sodium butyrate pretreatment reversed these changes. These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No. KIRAMS16-0002) on December 30, 2016.
引文
Autry AE,Monteggia LM(2012)Brain-derived neurotrophic factor and neuropsychiatric disorders.Pharmacol Rev 64:238-258.
Covington HE,Maze I,LaPlant QC,Vialou VF,Ohnishi YN,Berton O,Fass DM,Renthal W,Rush AJ,Wu EY,Ghose S,Krishnan V,Russo SJ,Tamminga C,Haggarty SJ,Nestler EJ(2009)Antidepressant actions of histone deacetylase inhibitors.J Neurosci29:11451-11460.
Crossen JR,Garwood D,Glatstein E,Neuwelt EA(1994)Neurobehavioral sequelae of cranial irradiation in adults:a review of radiation-induced encephalopathy.J Clin Oncol 12:627-642.
Davie JR(2003)Inhibition of histone deacetylase activity by butyrate.J Nutr 133:2485S-2493S.
Dinel AL,AndréC,Aubert A,Ferreira G,LayéS,Castanon N(2011)Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.PLoSOne 6:e24325.
Han A,Sung YB,Chung SY,Kwon MS(2014)Possible additional antidepressant-like mechanism of sodium butyrate:targeting the hippocampus.Neuropharmacology 81:292-302.
Johannesen TB,Lien HH,Hole KH,Lote K(2003)Radiological and clinical assessment of long-term brain tumor survivors after radiotherapy.Radiother Oncol 69:169-176.
Kempermann G,Kuhn HG,Gage FH(1997)Genetic influence on neurogenesis in the dentate gyrus of adult mice.Proc Natl Acad Sci U S A 94:10409-10414.
Kim JS,Lee HJ,Kim JC,Kang SS,Bae CS,Shin T,Jin JK,Kim SH,Wang H,Moon C(2008)Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.J Radiat Res 49:517-526.
Kim JS,Yang M,Cho J,Kim SH,Kim JC,Shin T,Moon C(2010)Promotion of cAMP responsive element-binding protein activity ameliorates radiation-induced suppression of hippocampal neurogenesis in adult mice.Toxicol Res 26:177-183.
Kim JS,Yang M,Kim SH,Shin T,Moon C(2013)Neurobiological toxicity of radiation in hippocampal cells.Histol Histopathol28:301-310.
Lazarov O,Hollands C(2016)Hippocampal neurogenesis:learning to remember.Prog Neurobiol 138-140:1-18.
Lee YW,Cho HJ,Lee WH,Sonntag WE(2012)Whole brain radiation-induced cognitive impairment:pathophysiological mechanisms and therapeutic targets.Biomol Ther 20:357-370.
Lin H,Geng X,Dang W,Wu B,Dai Z,Li Y,Yang Y,Zhang H,Shi J(2012)Molecular mechanisms associated with the antidepressant effects of the class I histone deacetylase inhibitor MS-275 in the rat ventrolateral orbital cortex.Brain Res 1447:119-125.
Meyers CA,Brown PD(2006)Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors.J Clin Oncol 24:1305-1309.
Minamiyama M,Katsuno M,Adachi H,Waza M,Sang C,Kobayashi Y,Tanaka F,Doyu M,Inukai A,Sobue G(2004)Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.Hum Mol Genet 13:1183-1192.
Nakagawa S,Kim JE,Lee R,Malberg JE,Chen J,Steffen C,Zhang YJ,Nestler EJ,Duman RS(2002)Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein.J Neurosci 22:3673-3682.
Raber J,Rola R,LeFevour A,Morhardt D,Curley J,Mizumatsu S,VandenBerg SR,Fike JR(2004)Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis.Radiat Res 162:39-47.
Schroeder FA,Lin CL,Crusio WE,Akbarian S(2007)Antidepressant-like effects of the histone deacetylase inhibitor,sodium butyrate,in the mouse.Biol Psychiatry 62:55-64.
Son Y,Yang M,Kang S,Lee S,Kim J,Kim J,Park S,Kim JS,Jo SK,Jung U,Shin T,Kim SH,Wang H,Moon C(2015a)Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus.Neurobiol Learn Mem121:12-19.
Son Y,Yang M,Kim JS,Kim J,Kim SH,Kim JC,Shin T,Wang H,Jo SK,Jung U,Moon C(2014)Hippocampal dysfunction during the chronic phase following a single exposure to cranial irradiation.Exp Neurol 254:134-144.
Son Y,Yang M,Wang H,Moon C(2015b)Hippocampal dysfunctions caused by cranial irradiation:a review of the experimental evidence.Brain Behav Immun 45:287-296.
van’t Spijker A,Trijsburg RW,Duivenvoorden HJ(1997)Psychological sequelae of cancer diagnosis:a meta-analytical review of58 studies after 1980.Psychosom Med 59:280-293.
Yang M,Kim J,Kim JS,Kim SH,Kim JC,Kang MJ,Jung U,Shin T,Wang H,Moon C(2014)Hippocampal dysfunctions in tumor-bearing mice.Brain Behav Immun 36:147-155.
Yang M,Kim JS,Song MS,Kim SH,Kang SS,Bae CS,Kim JC,Wang H,Shin T,Moon C(2010)Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice:possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits.Neurobiol Learn Mem 93:487-494.
Covington HE,Maze I,LaPlant QC,Vialou VF,Ohnishi YN,Berton O,Fass DM,Renthal W,Rush AJ,Wu EY,Ghose S,Krishnan V,Russo SJ,Tamminga C,Haggarty SJ,Nestler EJ(2009)Antidepressant actions of histone deacetylase inhibitors.J Neurosci29:11451-11460.
Crossen JR,Garwood D,Glatstein E,Neuwelt EA(1994)Neurobehavioral sequelae of cranial irradiation in adults:a review of radiation-induced encephalopathy.J Clin Oncol 12:627-642.
Davie JR(2003)Inhibition of histone deacetylase activity by butyrate.J Nutr 133:2485S-2493S.
Dinel AL,AndréC,Aubert A,Ferreira G,LayéS,Castanon N(2011)Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.PLoSOne 6:e24325.
Han A,Sung YB,Chung SY,Kwon MS(2014)Possible additional antidepressant-like mechanism of sodium butyrate:targeting the hippocampus.Neuropharmacology 81:292-302.
Johannesen TB,Lien HH,Hole KH,Lote K(2003)Radiological and clinical assessment of long-term brain tumor survivors after radiotherapy.Radiother Oncol 69:169-176.
Kempermann G,Kuhn HG,Gage FH(1997)Genetic influence on neurogenesis in the dentate gyrus of adult mice.Proc Natl Acad Sci U S A 94:10409-10414.
Kim JS,Lee HJ,Kim JC,Kang SS,Bae CS,Shin T,Jin JK,Kim SH,Wang H,Moon C(2008)Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.J Radiat Res 49:517-526.
Kim JS,Yang M,Cho J,Kim SH,Kim JC,Shin T,Moon C(2010)Promotion of cAMP responsive element-binding protein activity ameliorates radiation-induced suppression of hippocampal neurogenesis in adult mice.Toxicol Res 26:177-183.
Kim JS,Yang M,Kim SH,Shin T,Moon C(2013)Neurobiological toxicity of radiation in hippocampal cells.Histol Histopathol28:301-310.
Lazarov O,Hollands C(2016)Hippocampal neurogenesis:learning to remember.Prog Neurobiol 138-140:1-18.
Lee YW,Cho HJ,Lee WH,Sonntag WE(2012)Whole brain radiation-induced cognitive impairment:pathophysiological mechanisms and therapeutic targets.Biomol Ther 20:357-370.
Lin H,Geng X,Dang W,Wu B,Dai Z,Li Y,Yang Y,Zhang H,Shi J(2012)Molecular mechanisms associated with the antidepressant effects of the class I histone deacetylase inhibitor MS-275 in the rat ventrolateral orbital cortex.Brain Res 1447:119-125.
Meyers CA,Brown PD(2006)Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors.J Clin Oncol 24:1305-1309.
Minamiyama M,Katsuno M,Adachi H,Waza M,Sang C,Kobayashi Y,Tanaka F,Doyu M,Inukai A,Sobue G(2004)Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.Hum Mol Genet 13:1183-1192.
Nakagawa S,Kim JE,Lee R,Malberg JE,Chen J,Steffen C,Zhang YJ,Nestler EJ,Duman RS(2002)Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein.J Neurosci 22:3673-3682.
Raber J,Rola R,LeFevour A,Morhardt D,Curley J,Mizumatsu S,VandenBerg SR,Fike JR(2004)Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis.Radiat Res 162:39-47.
Schroeder FA,Lin CL,Crusio WE,Akbarian S(2007)Antidepressant-like effects of the histone deacetylase inhibitor,sodium butyrate,in the mouse.Biol Psychiatry 62:55-64.
Son Y,Yang M,Kang S,Lee S,Kim J,Kim J,Park S,Kim JS,Jo SK,Jung U,Shin T,Kim SH,Wang H,Moon C(2015a)Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus.Neurobiol Learn Mem121:12-19.
Son Y,Yang M,Kim JS,Kim J,Kim SH,Kim JC,Shin T,Wang H,Jo SK,Jung U,Moon C(2014)Hippocampal dysfunction during the chronic phase following a single exposure to cranial irradiation.Exp Neurol 254:134-144.
Son Y,Yang M,Wang H,Moon C(2015b)Hippocampal dysfunctions caused by cranial irradiation:a review of the experimental evidence.Brain Behav Immun 45:287-296.
van’t Spijker A,Trijsburg RW,Duivenvoorden HJ(1997)Psychological sequelae of cancer diagnosis:a meta-analytical review of58 studies after 1980.Psychosom Med 59:280-293.
Yang M,Kim J,Kim JS,Kim SH,Kim JC,Kang MJ,Jung U,Shin T,Wang H,Moon C(2014)Hippocampal dysfunctions in tumor-bearing mice.Brain Behav Immun 36:147-155.
Yang M,Kim JS,Song MS,Kim SH,Kang SS,Bae CS,Kim JC,Wang H,Shin T,Moon C(2010)Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice:possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits.Neurobiol Learn Mem 93:487-494.