リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Acute inhibition of AMPA receptors by perampanel reduces amyloid β-protein levels by suppressing β-cleavage of APP in Alzheimer's disease models」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Acute inhibition of AMPA receptors by perampanel reduces amyloid β-protein levels by suppressing β-cleavage of APP in Alzheimer's disease models

Ueda, Sakiho Kuzuya, Akira Kawata, Masayoshi Okawa, Kohei Honjo, Chika Wada, Takafumi Matsumoto, Mizuki Goto, Kazuya Miyamoto, Masakazu Yonezawa, Atsushi Tanabe, Yasuto Ikeda, Akio Kinoshita, Ayae Takahashi, Ryosuke 京都大学 DOI:10.1096/fj.202300837R

2023.11

概要

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aβ deposition in AD since enhanced neuronal activity promotes presynaptic Aβ production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aβ-evoked neuronal hyperexcitability, the acute effects of PER on Aβ metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aβ40 and Aβ42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aβ40 /Aβ42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER-treated J20 manifested a marked decrease in hippocampal APP βCTF levels with increased FL-APP levels. Consistently, acute treatment of PER reduced sAPPβ levels, a direct byproduct of β-cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aβ-induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aβ clearance, a γ-secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aβ, indicating that the acute effect of PER is predominantly on Aβ production. In conclusion, acute treatment of PER reduces Aβ production by suppressing β-cleavage of amyloid-β precursor protein effectively, indicating a potential effect of PER against Aβ pathology in AD.

この論文で使われている画像

参考文献

1. Masters CL, Simms G, Weinman NA, Multhaup G,

McDonald BL, Beyreuther K. Amyloid plaque core protein in

Alzheimer disease and Down syndrome. Proc Natl Acad Sci.

1985;82:4245-4249.

2. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's

disease: progress and problems on the road to therapeutics.

Science. 2002;297:353-356.

3. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992;256:184-185.

4. Sutphen CL, Jasielec MS, Shah AR, et al. Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age. JAMA Neurol. 2015;72:1029-1042.

5. Jonsson T, Atwal JK, Steinberg S, et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature. 2012;488:96-99.

6. Sjogren T, Sjogren H, Lindgren AG. Morbus Alzheimer and

morbus pick; a genetic, clinical and patho-anatomical study.

Acta Psychiatr Neurol Scand Suppl. 1952;82:1-152.

7. Förstl H, Burns A, Levy R, Cairns N, Luthert P, Lantos P. Neurologic

signs in Alzheimer's disease: results of a prospective clinical and

neuropathologic study. Arch Neurol. 1992;49:1038-1042.

8. Mendez MF, Catanzaro P, Doss RC, Arguello R, Frey WH.

Seizures in Alzheimer's disease: clinicopathologic study. J

Geriatr Psychiatry Neurol. 1994;7:230-233.

9. Mann DMA, Pickering-Brown SM, Takeuchi A, Iwatsubo T.

Amyloid angiopathy and variability in amyloid β deposition

is determined by mutation position in presenilin-1-linked

Alzheimer's disease. Am J Pathol. 2001;158:2165-2175.

10. Jayadev S, Leverenz JB, Steinbart E, et al. Alzheimer's disease

phenotypes and genotypes associated with mutations in presenilin 2. Brain. 2010;133:1143-1154.

11. Vossel KA, Beagle AJ, Rabinovici GD, et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA

Neurol. 2013;70:1158-1166.

12. Vossel KA, Ranasinghe KG, Beagle AJ, et al. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease.

Ann Neurol. 2016;80:858-870.

13. Lam AD, Deck G, Goldman A, Eskandar EN, Noebels J, Cole

AJ. Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease. Nat Med.

2017;23:678-680.

14. Vossel K, Ranasinghe KG, Beagle AJ, et al. Effect of levetiracetam on cognition in patients with Alzheimer disease with and

UEDA et al.

without epileptiform activity: a randomized clinical trial. JAMA

Neurol. 2021;78:1345-1354.

15. Bakker A, Albert MS, Krauss G, Speck CL, Gallagher M.

Response of the medial temporal lobe network in amnestic

mild cognitive impairment to therapeutic intervention assessed

by fMRI and memory task performance. NeuroImage: Clinical.

2015;7:688-698.

16. Bakker A, Krauss GL, Albert MS, et al. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron. 2012;74:467-474.

17. Koh MT, Haberman RP, Foti S, McCown TJ, Gallagher

M. Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment.

Neuropsychopharmacology. 2010;35:1016-1025.

18. 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. Proc Natl Acad

Sci. 2012;109:E2895-E2903.

19. Eddy CM, Rickards HE, Cavanna AE. The cognitive impact of

antiepileptic drugs. Ther Adv Neurol Disord. 2011;4:385-407.

20. Thompson P, Huppert FA, Trimble M. Phenytoin and cognitive

function: effects on normal volunteers and implications for epilepsy. Br J Clin Psychol. 1981;20:155-162.

21. Gallassi R, Morreale A, Lorusso S, Procaccianti G, Lugaresi

E, Baruzzi A. Carbamazepine and phenytoin: comparison of

cognitive effects in epileptic patients during monotherapy and

withdrawal. Arch Neurol. 1988;45:892-894.

22. Gallassi R, Morreale A, Di Sarro RA, Marra M, Lugaresi E,

Baruzzi A. Cognitive effects of antiepileptic drug discontinuation. Epilepsia. 1992;33(suppl 6):S41-S44.

23. Hessen E, Lossius MI, Reinvang I, Gjerstad L. Influence of major

antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind,

placebo-controlled withdrawal study of seizure-free epilepsy

patients receiving monotherapy. Epilepsia. 2006;47:2038-2045.

24. Park S-P, Kwon S-H. Cognitive effects of antiepileptic drugs. J

Cli Neurol (Seoul, Korea). 2008;4:99-106.

25. Taipale H, Gomm W, Broich K, et al. Use of antiepileptic

drugs and dementia risk—an analysis of Finnish health register and German health insurance data. J Am Geriatr Soc.

2018;66:1123-1129.

26. Li K-Y, Huang L-C, Chang Y-P, Yang Y-H. The effects of lacosamide on cognitive function and psychiatric profiles in patients

with epilepsy. Epilepsy Behav. 2020;113:107580.

27. Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat

Rev Neurosci. 2007;8:844-858.

28. Shankar GM, Li S, Mehta TH, et al. Amyloid-β protein dimers

isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med. 2008;14:837-842.

29. Klyubin I, Walsh DM, Lemere CA, et al. Amyloid beta protein

immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med. 2005;11:556-561.

30. Pellegrini-Giampietro DE, Gorter JA, Bennett MVL, Zukin

RS. The GluR2 (GluR-B) hypothesis: Ca2+−permeable

AMPA receptors in neurological disorders. Trends Neurosci.

1997;20:464-470.

31. Whitcomb DJ, Hogg EL, Regan P, et al. Intracellular oligomeric

amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus. Sci Rep. 2015;5:10934.

15306860, 2023, 11, Downloaded from https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202300837R by Cochrane Japan, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

16 of 18 32. Wei-Qin Z, Francesca S, Robert B, et al. Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors

prevents amyloid beta oligomer-induced synaptic disruption. J

Biol Chem. 2010;285(10):7619-7632.

33. Kim S, Ziff EB. Calcineurin mediates synaptic scaling via synaptic trafficking of Ca2+-permeable AMPA receptors. PLoS

Biol. 2014;12:e1001900.

34. Hettinger JC, Lee H, Bu G, Holtzman DM, Cirrito JR. AMPAergic regulation of amyloid-β levels in an Alzheimer's disease

mouse model. Mol Neurodegenerat. 2018;13:22.

35. Hanada T, Hashizume Y, Tokuhara N, et al. Perampanel: a

novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy.

Epilepsia. 2011;52:1331-1340.

36. Michael RA, Takahisa H. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist.

Acta Neurol Scand. 2013;127:19-24.

37. Carlson H, Ronne-Engström E, Ungerstedt U, Hillered L.

Seizure related elevations of extracellular amino acids in

human focal epilepsy. Neurosci Lett. 1992;140:30-32.

38. Matthew JD, Dennis DS. Extracellular hippocampal glutamate

and spontaneous seizure in the conscious human brain. Lancet

(London, England). 1993;341(8861):1607-1610.

39. Cendes F, Andermann F, Carpenter S, Zatorre RJ, Cashman

NR. Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor–mediated excitotoxicity

in humans. Ann Neurol. 1995;37:123-126.

40. Hanada T. Ionotropic glutamate receptors in epilepsy: a review focusing on AMPA and NMDA receptors. Biomolecules.

2020;10(3):464.

41. Bellingacci L, Tallarico M, Mancini A, et al. Non-competitive

AMPA glutamate receptors antagonism by perampanel as a

strategy to counteract hippocampal hyper-excitability and cognitive deficits in cerebral amyloidosis. Neuropharmacology.

2023;225:109373.

42. Inoue Y, Sumitomo K, Matsutani K, Ishii M. Evaluation of real-world effectiveness of perampanel in Japanese adults and

older adults with epilepsy. Epileptic Disord. 2021;24:123-132.

43. Lattanzi S, Cagnetti C, Foschi N, et al. Adjunctive perampanel

in older patients with epilepsy: a multicenter study of clinical

practice. Drugs Aging. 2021;38:603-610.

44. Watanabe T, Osugi S, Soba T. Usefulness of long-term administration of perampanel in the treatment of elderly-onset epilepsy secondary to Alzheimer dementia. J new Remedies Clin.

2021;68:990-1003.

45. Gilbert J, Shu S, Yang X, Lu Y, Zhu L-Q, Man H-Y. β-Amyloid

triggers aberrant over-scaling of homeostatic synaptic plasticity. Acta Neuropathol Commun. 2016;4:1-14.

46. Cirrito JR, May PC, O'Dell MA, et al. In vivo assessment of

brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J

Neurosci. 2003;23:8844-8853.

47. Kuzuya A, Zoltowska KM, Post KL, et al. Identification of the

novel activity-driven interaction between synaptotagmin 1 and

presenilin 1 links calcium, synapse, and amyloid beta. BMC

Biol. 2016;14:25.

48. Miyamoto M, Kuzuya A, Noda Y, et al. Synaptic vesicle protein 2B negatively regulates the Amyloidogenic processing of

17 of 18

49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. AβPP as a novel interaction partner of BACE1. J Alzheimers Dis.

2020;75:173-185.

Zhao T, Yu L-H, Zhang H-L, et al. Development and application

of a novel LC–MS/MS method for human plasma concentration monitoring of perampanel in pediatric epilepsy patients.

Biomed Chromatogr. 2022;36:e5446.

Mucke L, Masliah E, Yu GQ, et al. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation.

J Neurosci. 2000;20:4050-4058.

Wright AL, Zinn R, Hohensinn B, et al. Neuroinflammation

and neuronal loss precede Aβ plaque deposition in the

hAPP-J20 mouse model of Alzheimer's disease. PLoS ONE.

2013;8:e59586.

Maesako M, Uemura K, Iwata A, et al. Continuation of exercise

is necessary to inhibit high fat diet-induced β-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice. PLoS ONE. 2013;8:e72796.

Cheng IH, Scearce-Levie K, Legleiter J, et al. Accelerating amyloid-β fibrillization reduces oligomer levels and functional

deficits in Alzheimer disease mouse models. J Biol Chem.

2007;282:23818-23828.

Saganich MJ, Schroeder BE, Galvan V, Bredesen DE, Koo EH,

Heinemann SF. Deficits in synaptic transmission and learning

in amyloid precursor protein (APP) transgenic mice require

C-terminal cleavage of APP. J Neurosci. 2006;26:13428-13436.

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.

Neuron. 2007;55:697-711.

Bezzina C, Verret L, Juan C, et al. Early onset of hypersynchronous network activity and expression of a marker of chronic

seizures in the Tg2576 mouse model of Alzheimer's disease.

PLoS ONE. 2015;10:e0119910.

Kam K, Duffy Á, Moretto J, LaFrancois JJ, Scharfman HE.

Interictal spikes during sleep are an early defect in the

Tg2576 mouse model of β-amyloid neuropathology. Sci Rep.

2016;6:20119.

Busche MA, Chen X, Henning HA, et al. Critical role of soluble

amyloid-β for early hippocampal hyperactivity in a mouse model

of Alzheimer's disease. Proc Natl Acad Sci. 2012;109:8740-8745.

Hong S, Quintero-Monzon O, Ostaszewski BL, et al. Dynamic

analysis of amyloid β-protein in behaving mice reveals opposing changes in ISF versus parenchymal Aβ during age-related

plaque formation. J Neurosci. 2011;31:15861-15869.

Yamamoto Y, Usui N, Nishida T, et al. Therapeutic drug monitoring for Perampanel in Japanese epilepsy patients: influence of concomitant antiepileptic drugs. Ther Drug Monit.

2017;39:446-449.

Shi S-H. AMPA receptor dynamics and synaptic plasticity.

Science. 2001;294:1851-1852.

Isaac JTR, Ashby MC, McBain CJ. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron.

2007;54:859-871.

Lodge D. The history of the pharmacology and cloning of ionotropic glutamate receptors and the development of idiosyncratic nomenclature. Neuropharmacology. 2009;56:6-21.

Hayashi Y, Shi S-H, Esteban JA, Piccini A, Poncer J-C, Malinow

R. Driving AMPA receptors into synapses by LTP and CaMKII:

15306860, 2023, 11, Downloaded from https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202300837R by Cochrane Japan, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

UEDA et al.

requirement for GluR1 and PDZ domain interaction. Science.

2000;287:2262-2267.

65. Passafaro M, Piëch V, Sheng M. Subunit-specific temporal and

spatial patterns of AMPA receptor exocytosis in hippocampal

neurons. Nat Neurosci. 2001;4:917-926.

66. Granger AJ, Shi Y, Lu W, Cerpas M, Nicoll RA. LTP requires

a reserve pool of glutamate receptors independent of subunit

type. Nature. 2013;493:495-500.

67. Buonarati OR, Hammes EA, Watson JF, Greger IH, Hell JW.

Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation. Sci Signal. 2019;12:eaar6889.

68. Busche MA, Eichhoff G, Adelsberger H, et al. Clusters of hyperactive neurons near amyloid plaques in a mouse model of

Alzheimer's disease. Science. 2008;321:1686-1689.

69. Zott B, Simon MM, Hong W, et al. A vicious cycle of β amyloid–dependent neuronal hyperactivation. Science. 2019;365:​

559-565.

70. Kamenetz F, Tomita T, Hsieh H, et al. APP processing and synaptic function. Neuron. 2003;37:925-937.

71. Lesné S, Ali C, Gabriel C, et al. NMDA receptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta

production. J Neurosci. 2005;25:9367-9377.

72. Cirrito JR, Yamada KA, Finn MB, et al. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron.

2005;48:913-922.

73. Cirrito JR, Kang JE, Lee J, et al. Endocytosis is required for

synaptic activity-dependent release of amyloid-beta in vivo.

Neuron. 2008;58:42-51.

74. Hoe H-S, Fu Z, Makarova A, et al. The effects of amyloid precursor protein on postsynaptic composition and activity. J Biol

Chem. 2009;284:8495-8506.

75. Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer's disease:

evidence for a relationship between default activity, amyloid,

and memory. J Neurosci. 2005;25:7709-7717.

76. Mackenzie IRA, McLachlan RS, Kubu CS, Miller LA.

Prospective neuropsychological assessment of nondemented

patients with biopsy proven senile plaques. Neurology.

1996;46:425-429.

77. Gourmaud S, Shou H, Irwin DJ, et al. Alzheimer-like amyloid

and tau alterations associated with cognitive deficit in temporal

lobe epilepsy. Brain. 2020;143:191-209.

78. Zilles K, Qü MS, Köhling R, Speckmann EJ. Ionotropic glutamate and GABA receptors in human epileptic neocortical tissue: quantitative in vitro receptor autoradiography.

Neuroscience. 1999;94:1051-1061.

79. Graebenitz S, Kedo O, Speckmann E-J, et al. Interictal-like network activity and receptor expression in the epileptic human

lateral amygdala. Brain. 2011;134:2929-2947.

80. Çavuş I, Romanyshyn JC, Kennard JT, et al. Elevated basal

glutamate and unchanged glutamine and GABA in refractory

epilepsy: microdialysis study of 79 patients at the yale epilepsy

surgery program. Ann Neurol. 2016;80:35-45.

81. Marcello E, Epis R, Saraceno C, et al. SAP97-mediated local

trafficking is altered in Alzheimer disease patients' hippocampus. Neurobiol Aging. 2012;33:422.e1.

UEDA et al.

82. Bero AW, Yan P, Roh JH, et al. Neuronal activity regulates the

regional vulnerability to amyloid-β deposition. Nat Neurosci.

2011;14:750-756.

83. Del Prete D, Lombino F, Liu X, D'Adamio L. APP is cleaved by Bace1

in pre-synaptic vesicles and establishes a pre-synaptic Interactome,

via its intracellular domain, with molecular complexes that regulate pre-synaptic vesicles functions. PloS One. 2014;9:e108576.

84. Hoey SE, Buonocore F, Cox CJ, Hammond VJ, Perkinton MS,

Williams RJ. AMPA receptor activation promotes non-amyloidogenic amyloid precursor protein processing and suppresses

neuronal amyloid-β production. PloS One. 2013;8:e78155.

85. Toledano Delgado R, García-Morales I, Parejo-Carbonell B,

et al. Effectiveness and safety of perampanel monotherapy for

focal and generalized tonic-clonic seizures: experience from a

national multicenter registry. Epilepsia. 2020;61:1109-1119.

86. Leppik IE, Wechsler RT, Williams B, Yang H, Zhou S, Laurenza

A. Efficacy and safety of perampanel in the subgroup of elderly patients included in the phase III epilepsy clinical trials.

Epilepsy Res. 2015;110:216-220.

87. Liguori C, Izzi F, Manfredi N, et al. Efficacy and tolerability of

perampanel and levetiracetam as first add-on therapy in patients with epilepsy: a retrospective single center study. Epilepsy

Behav. 2018;80:173-176.

88. Snoeijen-Schouwenaars FM, van Ool JS, Tan IY, Schelhaas HJ,

Majoie MHJM. Evaluation of perampanel in patients with intellectual disability and epilepsy. Epilepsy Behav. 2017;66:64-67.

89. Kumamoto A, Chiba Y, Suda A, Hishimoto A, Kase A. A severe

dementia case in end of life care with psychiatric symptoms

treated by perampanel. J Epilepsy Res. 2021;11:93-95.

90. Bektas N, Arslan R, Alyu F. The anxiolytic effect of perampanel

and possible mechanisms mediating its anxiolytic effect in

mice. Life Sci. 2020;261:118359.

91. Helmstaedter C, Witt J-A. Epilepsy and cognition—a bidirectional relationship? Seizure-Eur J Epilep. 2017;49:83-89.

92. Yamada K, Iwatsubo T. Extracellular α-synuclein levels are regulated by neuronal activity. Mol Neurodegenerat. 2018;13:9.

93. Ueda J, Uemura N, Sawamura M, et al. Perampanel inhibits

α-Synuclein transmission in Parkinson's disease models. Mov

Disord. 2021;36:1554-1564.

94. Yamada K, Holth JK, Liao F, et al. Neuronal activity regulates

extracellular tau in vivo. J Exp Med. 2014;211:387-393.

95. Monteiro-Fernandes D, Silva JM, Soares-Cunha C, et al.

Allosteric modulation of AMPA receptors counteracts Taurelated excitotoxic synaptic signaling and memory deficits in

stress- and Aβ-evoked hippocampal pathology. Mol Psychiatry.

2021;26:5899-5911.

How to cite this article: Ueda S, Kuzuya A,

Kawata M, et al. Acute inhibition of AMPA

receptors by perampanel reduces amyloid β-protein

levels by suppressing β-cleavage of APP in

Alzheimer's disease models. The FASEB Journal.

2023;37:e23252. doi:10.1096/fj.202300837R

15306860, 2023, 11, Downloaded from https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202300837R by Cochrane Japan, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

18 of 18 ...

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る