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中华神经创伤外科电子杂志 ›› 2015, Vol. 01 ›› Issue (04) : 232 -236. doi: 10.3877/cma.j.issn.2095-9141.2015.04.010

专题笔谈

神经超兴奋性与阿尔茨海默病
张茂营1, 贾伟强2, 马全红3, 徐如祥2,()   
  1. 1.510630 广州,暨南大学附属第一医院神经外科
    2.100700 北京,北京军区总医院神经外科研究
    3.215021 苏州,苏州大学神经科学研究所
  • 收稿日期:2015-04-08 出版日期:2015-08-15
  • 通信作者: 徐如祥
  • 基金资助:
    国家自然基金项目(81500915,BWS11J002)广东省自然科学基金-博士启动项目(408203555024)暨南大学科研培育与创新基金研究项目(21615336)

Neural network hyperactivity in Alzheimer’s disease

Maoying Zhang1, Weiqiang Jia2, Quanhong Ma3, Ruxiang Xu2,()   

  1. 1.Department of Neurosurgery,The First Affiliated Hospital of Jinan University,Guangzhou 510630,China
    2.Affiliated Bayi Brain Hospital,The Military General Hospital of Beijing PLA,Beijing 100700,China
    3.Institute of Neuroscience,Soochow University,Suzhou 215021,China
  • Received:2015-04-08 Published:2015-08-15
  • Corresponding author: Ruxiang Xu
引用本文:

张茂营, 贾伟强, 马全红, 徐如祥. 神经超兴奋性与阿尔茨海默病[J]. 中华神经创伤外科电子杂志, 2015, 01(04): 232-236.

Maoying Zhang, Weiqiang Jia, Quanhong Ma, Ruxiang Xu. Neural network hyperactivity in Alzheimer’s disease[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2015, 01(04): 232-236.

阿尔茨海默病(AD)是一种常见的神经系统疾病,其病因和发病机制尚无满意阐述,治疗上也因存在许多瓶颈而无肯定有效的措施。近年来,研究发现在AD患者及动物模型脑内表现出更高的癫痫发生率或异常的脑电节律,这种异常神经网络活动与AD认知损害密切相关。近些年来研究发现AD转基因小鼠脑内异常神经网络活动是导致突触功能受损、认知功能损害以及行为异常的上游机制,抗癫痫药物(左乙拉西坦)通过调控钠离子电压门控通道能抑制AD转基因模型鼠脑内这种异常的神经网络活动,恢复异常的突触功能,改善其认知能力。抗癫痫药对AD治疗的有效性引起广泛关注。本文就神经超兴奋性与AD的关系及其治疗进展作一综述。

Alzheimers Disease(AD)is a common neurological disease,whose specific pathogenesis is still unclear.There are still no effective treatments to prevent,halt,or reverse Alzheimer’s disease.AD patients have an increase dincidence of epileptic seizures.Hyperexcitability has also been observed in various AD transgenic mice.Such aberrant network activity is closely related to cognitive deficits and the pathogenesis of AD.Recent studies suggest that the aberrant network activity is upstream and contributes causally to synaptic,cognitive,and behavioral dysfunctions in AD transgenic mice.Blocking the network hyperactivity with LEV,an antiepileptic drugs(AEDs),which inhibits voltage-dependent sodium channels,reversed synaptic dysfunction and cognitive deficits in hAPPmice.These studies have been paid great attention,especially the potential application of AEDs,in AD therapy.This Review highlights the relationship between the aberrant network activity and AD in AD research,and raises major unresolved issues,especially the potential application of AEDs,in AD therapy.

[1]
Selkoe DJ.Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein[J].Journal of Alzheimer'sdisease,2001,3(1):75-80.
[2]
Amatniek JC,Hauser WA,DelCastillo-Castaneda C,et al.Incidence and predictors of seizures in patients with Alzheimer's disease[J].Epilepsia,2006,47(5):867-872.
[3]
Palop JJ,Mucke L.Epilepsy and cognitive impairments in Alzheimer disease[J].Archives of neurology.2009,66(4):435-440.
[4]
Harris JA,Devidze N,Verret L,et al.Transsynaptic progression of amyloid-beta-induced neuronal dysfunction within the entorhinal-hippocampal network[J].Neuron,2010,68(3):428-441.
[5]
Minkeviciene R,Rheims S,Dobszay MB,et al.Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy[J].The Journal of Neuroscience,2009,29(11):3453-3462.
[6]
Roberson ED,Halabisky B,Yoo JW,et al.Amyloid-beta/Fyninduced synaptic,network,and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease[J].The Journal of Neuroscience,2011,31(2):700-711.
[7]
Palop JJ,Chin J,Roberson ED,et al.Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease[J].Neuron,2007,55(5):697-711.
[8]
Vogt DL,Thomas D,Galvan V,et al.Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain[J].Neurobiology of aging,2011,32(9):1725-1729.
[9]
Ziyatdinova S,Gurevicius K,Kutchiashvili N,et al.Spontaneous epileptiform discharges in a mouse model of Alzheimer's disease are suppressed by antiepileptic drugs that block sodium channels[J].Epilepsy research,2011,94(1-2):75-85.
[10]
Sanchez PE,Zhu L,Verret L,et al.Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model[J].Proc Natl Acad Sci USA,2012,109(42):2895-2903.
[11]
Cumbo E,Ligori LD.Levetiracetam,lamotrigine,and phenobarbital in patients withepileptic seizures and Alzheimer’sdisease[J].Epilepsy Behav,2010,17(4):461-466.
[12]
Huang Y,Mucke L.Alzheimer mechaisms and therapeutic strategies[J].Cell,2012,148(6):1204-1222.
[13]
Cai H,Wang D,McCarthy H,et al.BACE1 is the major beta-secretase for generation of Abeta peptides by neurons[J].Nat Neurosci,2001,4(3):233-234.
[14]
Hsieh H,Boehm J,Sato C,et al.AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss[J].Neuron,2006,52(5):831-843.
[15]
Palop J.J,Chin J,Mucke L.A network dysfunction perspective on neurodegenerative diseases[J].Nature,2006,443(7113):768-773.
[16]
Verret L,Mann EO,Hang GB,et al.Inhibitory interneuron de ficit links altered networkactivity and cognitive dysfunction in Alzheimer model[J].Cell,2012,149(3):708-721.
[17]
Meilandt WJ,Yu GQ,Chin J,et al.Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer’s disease[J].J.Neurosci,28(19):5007-5017.
[18]
Palop JJ,Jones B,Kekonius L,et al.Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits[J].Proc Natl Acad Sci U SA,2003,100(16):9572-9577.
[19]
Palop JJ,Chin J,Bien Ly N,et al.Vulnerability of dentate granule cells to disruption of Arc expressionin human amyloid precursor protein transgenic mice[J].J Neurosci,2005,25(42):9686-9693.
[20]
Chin J,Palop JJ,Puoliväli J,et al.Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer'sdisease[J].JNeurosci,2005,25(42):9694-9703.
[21]
Bero AW,Yan P,Roh JH,et al.Neuronal activity regulates the regional vulnerability to amyloid deposition[J].Nat Neurosci,2011,14(6):750-756.
[22]
Hong Qing,Guiqiong He,PhilipT.T.Ly,et al.Valproic acid inhibits Aβproduction,neuritic plaque formation,and behavioral deifcits in Alzheimer’s disease mouse models[J].J.Exp.Med,2008,205(12):2781-2789.
[23]
The Alzheimer disease and frontotemporal dementia mutation database.Flanders Interuniversity Institute for Biotechnology Department of Molecular Genetics Web site;2008.
[24]
Amatniek JC,Hauser WA,Delcastillo-Castaneda C,et al.Incidence and predictors of seizures in patients with Alzheimer’sdisease[J].Epilepsia,2006,47(5):867-872.
[25]
Larner AJ,Doran M.Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of thepresenilin-1 gene[J].JNeurol,2006,253(2):139-158.
[26]
Snider BJ,Norton J,Coats MA,et al.Novel presenilin 1 mutation(S170F)causing Alzheimer disease with Lewy bodies in the third decade of life[J].Arch Neurol,2005,62(12):1821-1830.
[27]
Palop JJ,Mucke L.Amyloid-βInduced Neuronal Dysfunction in Alzheimer’s Disease:From Synapses toward Neural Networks[J].Nat Neurosci,2010,13(7):812-818.
[28]
Mahley RW,Weisgraber KH,Huang Y.Apolipoprotein E4:a causative factor and therapeutic target in neuropathology,including Alzheimer's disease[J].Proc Natl Acad Sci U S A,2006,103(15):5644-5651.
[29]
Ponomareva NV,Korovaitseva GI,Rogaev EI.EEG alterations in non-demented individuals related to apolipoprotein E genotype and to risk of Alzheimer disease[J].Neurobiol Aging,2008,29(6):819-827.
[30]
Ponomareva NV,Selesneva ND,Jarikov GA.EEG alterations in subjects at high familial risk for Alzheimer's disease.Neuropsychobiology,2003,48(3):152-159.
[31]
Vossel KA,Beagle AJ,Rabinovici GD,et al.Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease[J].JAMA Neurol,2013,70(9):1158-1566.
[32]
Koh MT,Haberman RP,Foti S,et al.Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment[J].Neuropsychopharmacology,2010,35(4):1016-1025.
[33]
Bakker A,Krauss GL,Albert MS,et al.Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitiveimpairment[J].Neuron,2012,74(3):467-474.
[34]
Cumbo E,Ligori LD.Levetiracetam,lamotrigine,and phenobarbital in patients withepileptic seizures and Alzheimer’sdisease[J].Epilepsy Behav,2010,17(4):461-466.
[35]
Mendez M,Lim G.Seizures in elderly patients with dementia:epidemiology and management[J].Drugs Aging,2003,20(11):791-803.
[36]
Fleisher AS,Truran D,Mai JT,et al.Alzheimer’s Disease Cooperative Study.Chronic divalproex sodium use and brain atrophy in Alzheimer disease[J].Neurology,2011,77(13):1263-1271.
[37]
Tariot PN,Schneider LS,Cummings J,et al.Alzheimer’s Disease Cooperative Study Group.Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease[J].Arch Gen Psychiatry,2011,68(8):853-861.
[38]
Irizarry MC,Jin S,He F,et al.Incidence of new-onset seizures in mild to moderate Alzheimer disease[J].Arch Neurol,2012,69(3):368-372.
[39]
Bakker A,Krauss GL,Albert MS,et al.Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitiveimpairment[J].Neuron,2012,74(3):467-474.
[40]
Meehan AL,Yang X,McAdams BD,et al.A new mechanism for antiepileptic drug action:vesicular entry may mediate the effects of levetiracetam[J].J Neurophysiol,2011,106(3):1227-1239.
[41]
Shi JQ,Wang BR,Tian YY,et al.Antiepileptics topiramate and levetiracetam alleviate behavioral deficits and reduce neuropathology in APPswe/PS1dE9 transgenic mice[J].CNS Neurosci Ther,2013,19(11):871-881.
[42]
Cardinale JP,Sriramula S,Pariaut R,et al.HDAC inhibition attenuates inflammatory,hypertrophic,and hypertensive responses in spontaneously hypertensive rats[J].Hypertension,2010,56(3):437-444.
[43]
Kochanek AR,Fukudome EY,Li Y,et al.Histone deacetylase inhibitor treatment attenuates MAP kinase pathway activation and pulmonary inflammation following hemorrhagic shock in a rodent model[J].JSurg Res2011,176(1):185-194.
[44]
Kim HJ,Rowe M,Ren M,et al.Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke:Multiple mechanisms of action[J].JPharmacol Exp Ther,2007,321(3):892-901.
[45]
Suh HS,Choi S,Khattar P,et al.Histone deacetylase inhibitors suppress the expression of inflammatory and innate immune response genes in human microglia and astrocytes[J].J Neuroimmune Pharmacol,2010,5(4):521-532.
[46]
Mark RJ,Ashford JW,Goodman Y,et al.Anticonvulsants attenuate amyloid beta-peptide neurotoxicity,Ca2+deregulation,and cytoskeletalpathology[J].Neurobiol Aging,1995,16(2):187-198.
[47]
Angehagen M,Margineanu DG,Ben-Menachem E,et al.Levetiracetam reduces caffeine-induced Ca2+transients and epileptiform potentials in hippocampal neurons[J].Neuroreport,2003,14(3):471-475.
[48]
Pisani A,Bonsi P,Martella G,et al.Intracellular calcium increase in epileptiform activity:Modulation by levetiracetam and lamotrigine[J].Epilepsia,2004,45(7):719-728.
[49]
Chen PS,Wang CC,Bortner CD,et al.Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide induced dopaminergic neurotoxicity[J].Neuroscience,2007,149(1):203-212.
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