表观遗传修饰对突触可塑性的调控作用研究进展
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摘要
突触可塑性被认为是学习记忆细胞水平的生物学基础,与学习记忆密切相关。最近的研究表明,表观遗传修饰如DNA甲基化和组蛋白翻译后修饰在调节突触可塑性中发挥重要作用,这一发现不仅有助于进一步阐释学习记忆复杂的机制,更有利于为记忆相关疾病的诊治提供新思路。论文介绍了表观遗传修饰机制的基本背景,并就表观遗传修饰在调控突触可塑性及认知功能障碍中的作用进行综述。
Synaptic plasticity is considered to be the biological basis of learning and memory at the cellular level,and is closely related to learning and memory.Recent studies have shown that epigenetic mechanisms such as DNA methylation and histone post-translational modifications play an important role in the regulation of synaptic plasticity.This finding will not only help to explain the complex mechanism of learning and memory,but also provide new ideas to the diagnosis and treatment of memory-related diseases.This paper introduced the basic concept of epigenetic modification mechanism,and mainly focused on the role of epigenetic modification in the regulation of synaptic plasticity and cognitive dysfunction in recent years.
Synaptic plasticity is considered to be the biological basis of learning and memory at the cellular level,and is closely related to learning and memory.Recent studies have shown that epigenetic mechanisms such as DNA methylation and histone post-translational modifications play an important role in the regulation of synaptic plasticity.This finding will not only help to explain the complex mechanism of learning and memory,but also provide new ideas to the diagnosis and treatment of memory-related diseases.This paper introduced the basic concept of epigenetic modification mechanism,and mainly focused on the role of epigenetic modification in the regulation of synaptic plasticity and cognitive dysfunction in recent years.
引文
[1]Hegde A N.Proteolysis,synaptic plasticity and memory[J].Neurobiol Learn Mem,2017,138:98-110.
[2]Kim M,Costello J.DNA methylation:an epigenetic mark of cellular memory[J].Exp Mol Med,2017,49(4):e322.
[3]McCamphill P K,Ferguson L,Sossin W S.A decrease in eukaryotic elongation factor 2phosphorylation is required for local translation of sensorin and long-term facilitation in Aplysia[J].J Neurochem,2017,142(2):246-259.
[4]Kandel E R.The molecular biology of memory storage:a dialogue between genes and synapses[J].Science,2001,294(5544):1030-1038.
[5]Guan Z,Giustetto M,Lomvardas S,et al.Integration of longterm-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure[J].Cell,2002,111(4):483-493.
[6]Nicoll R A.A brief history of long-term potentiation[J].Neuron,2017,93(2):281-290.
[7]Alarcón J M,Malleret G,Touzani K,et al.Chromatin acetylation,memory,and LTP are impaired in CBP+/-mice:a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration.[J].Neuron,2004,42(6):947-959.
[8]Barrett R M,Malvaez M,Kramar E,et al.Hippocampal focal knockout of CBP affects specific histone modifications,longterm potentiation,and long-term memory[J].Neuropsychopharmacology,2011,36(8):1545-1556.
[9]Yeh S H,Lin C H,Gean P W.Acetylation of nuclear factorkappaB in rat amygdala improves long-term but not short-term retention of fear memory[J].Mol Pharmacol,2004,65(5):1286-1292.
[10]Vecsey C G,Hawk J D,Lattal K M,et al.Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation[J].J Neurosci,2007,27(23):6128-6140.
[11]Guan J S,Haggarty S J,Giacometti E,et al.HDAC2negatively regulates memory formation and synaptic plasticity[J].Nature,2009,459(7243):55-60.
[12]Halder R,Hennion M,Vidal R O,et al.DNA methylation changes in plasticity genes accompany the formation and maintenance of memory[J].Nat Neurosci,2016,19(1):102-110.
[13]Munoz P,Estay C,Diaz P,et al.Inhibition of DNA methylation impairs synaptic plasticity during an early time window in rats[J].Neural Plast,2016,2016:4783836.
[14]Meadows J P,Guzman-Karlsson M C,Phillips S,et al.DNA methylation regulates neuronal glutamatergic synaptic scaling[J].Sci Signal,2015,8(382):ra61.
[15]Levenson J M,Roth T L,Lubin F D,et al.Evidence that DNA(cytosine-5)methyltransferase regulates synaptic plasticity in the hippocampus[J].J Biol Chem,2006,281(23):15763-15773.
[16]Scott H,Smith A E,Barker G R,et al.Contrasting roles for DNA methyltransferases and histone deacetylases in single-item and associative recognition memory[J].Neuroepigenetics,2017,9:1-9.
[17]Feng J,Zhou Y,Campbell S L,et al.Dnmt1and Dnmt3amaintain DNA methylation and regulate synaptic function in adult forebrain neurons[J].Nat Neurosci,2010,13(4):423-430.
[18]Chahrour M,Jung S Y,Shaw C,et al.MeCP2,a key contributor to neurological disease,activates and represses transcription[J].Science,2008,320(5880):1224-1229.
[19]Gupta S,Kim S Y,Artis S,et al.Histone methylation regulates memory formation[J].J Neurosci,2010,30(10):3589-3599.
[20]Chouliaras L,Mastroeni D,Delvaux E,et al.Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients[J].Neurobiol Aging,2013,34(9):2091-2099.
[21]Coppieters N,Dieriks B V,Lill C,et al.Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain[J].Neurobiol Aging,2014,35(6):1334-1344.
[22]Ricobaraza A,Cuadrado-Tejedor M,Perez-Mediavilla A,et al.Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model[J].Neuropsychopharmacology,2009,34(7):1721-1732.
[23]Ricobaraza A,Cuadrado-Tejedor M,Marco S,et al.Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease[J].Hippocampus,2012,22(5):1040-1050.
[24]Kilgore M,Miller C A,Fass D M,et al.Inhibitors of class 1histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease[J].Neuropsychopharmacology,2010,35(4):870-880.
[25]Francis Y I,Fa M,Ashraf H,et al.Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer's disease[J].J Alzheimers Dis,2009,18(1):131-139.
[2]Kim M,Costello J.DNA methylation:an epigenetic mark of cellular memory[J].Exp Mol Med,2017,49(4):e322.
[3]McCamphill P K,Ferguson L,Sossin W S.A decrease in eukaryotic elongation factor 2phosphorylation is required for local translation of sensorin and long-term facilitation in Aplysia[J].J Neurochem,2017,142(2):246-259.
[4]Kandel E R.The molecular biology of memory storage:a dialogue between genes and synapses[J].Science,2001,294(5544):1030-1038.
[5]Guan Z,Giustetto M,Lomvardas S,et al.Integration of longterm-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure[J].Cell,2002,111(4):483-493.
[6]Nicoll R A.A brief history of long-term potentiation[J].Neuron,2017,93(2):281-290.
[7]Alarcón J M,Malleret G,Touzani K,et al.Chromatin acetylation,memory,and LTP are impaired in CBP+/-mice:a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration.[J].Neuron,2004,42(6):947-959.
[8]Barrett R M,Malvaez M,Kramar E,et al.Hippocampal focal knockout of CBP affects specific histone modifications,longterm potentiation,and long-term memory[J].Neuropsychopharmacology,2011,36(8):1545-1556.
[9]Yeh S H,Lin C H,Gean P W.Acetylation of nuclear factorkappaB in rat amygdala improves long-term but not short-term retention of fear memory[J].Mol Pharmacol,2004,65(5):1286-1292.
[10]Vecsey C G,Hawk J D,Lattal K M,et al.Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation[J].J Neurosci,2007,27(23):6128-6140.
[11]Guan J S,Haggarty S J,Giacometti E,et al.HDAC2negatively regulates memory formation and synaptic plasticity[J].Nature,2009,459(7243):55-60.
[12]Halder R,Hennion M,Vidal R O,et al.DNA methylation changes in plasticity genes accompany the formation and maintenance of memory[J].Nat Neurosci,2016,19(1):102-110.
[13]Munoz P,Estay C,Diaz P,et al.Inhibition of DNA methylation impairs synaptic plasticity during an early time window in rats[J].Neural Plast,2016,2016:4783836.
[14]Meadows J P,Guzman-Karlsson M C,Phillips S,et al.DNA methylation regulates neuronal glutamatergic synaptic scaling[J].Sci Signal,2015,8(382):ra61.
[15]Levenson J M,Roth T L,Lubin F D,et al.Evidence that DNA(cytosine-5)methyltransferase regulates synaptic plasticity in the hippocampus[J].J Biol Chem,2006,281(23):15763-15773.
[16]Scott H,Smith A E,Barker G R,et al.Contrasting roles for DNA methyltransferases and histone deacetylases in single-item and associative recognition memory[J].Neuroepigenetics,2017,9:1-9.
[17]Feng J,Zhou Y,Campbell S L,et al.Dnmt1and Dnmt3amaintain DNA methylation and regulate synaptic function in adult forebrain neurons[J].Nat Neurosci,2010,13(4):423-430.
[18]Chahrour M,Jung S Y,Shaw C,et al.MeCP2,a key contributor to neurological disease,activates and represses transcription[J].Science,2008,320(5880):1224-1229.
[19]Gupta S,Kim S Y,Artis S,et al.Histone methylation regulates memory formation[J].J Neurosci,2010,30(10):3589-3599.
[20]Chouliaras L,Mastroeni D,Delvaux E,et al.Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients[J].Neurobiol Aging,2013,34(9):2091-2099.
[21]Coppieters N,Dieriks B V,Lill C,et al.Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain[J].Neurobiol Aging,2014,35(6):1334-1344.
[22]Ricobaraza A,Cuadrado-Tejedor M,Perez-Mediavilla A,et al.Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model[J].Neuropsychopharmacology,2009,34(7):1721-1732.
[23]Ricobaraza A,Cuadrado-Tejedor M,Marco S,et al.Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease[J].Hippocampus,2012,22(5):1040-1050.
[24]Kilgore M,Miller C A,Fass D M,et al.Inhibitors of class 1histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease[J].Neuropsychopharmacology,2010,35(4):870-880.
[25]Francis Y I,Fa M,Ashraf H,et al.Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer's disease[J].J Alzheimers Dis,2009,18(1):131-139.