[논문]β-Amyrin Ameliorates Alzheimer's Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus

Park, Hye Jin; Kwon, Huiyoung; Lee, Ji Hye; Cho, Eunbi; Lee, Young Choon; Moon, Minho; Jun, Mira; Kim, Dong Hyun; Jung, Ji Wook

doi:10.4062/biomolther.2019.024

β-Amyrin Ameliorates Alzheimer's Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus 원문보기

Biomolecules & therapeutics, v.28 no.1, 2020년, pp.74 - 82

Park, Hye Jin (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) , Kwon, Huiyoung (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) , Lee, Ji Hye (Division of Endocrinology, School of Medicine, Kyungpook National University) , Cho, Eunbi (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) , Lee, Young Choon (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) , Moon, Minho (Department of Biochemistry, College of Medicine, Konyang University) , Jun, Mira (Institute of Convergence Bio-Health, Dong-A University) , Kim, Dong Hyun (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) , Jung, Ji Wook (Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University)

Abstract ▼ AI-Helper

Alzheimer's disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling. LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.

주제어

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가설 설정

To test whether β-amyrin ameliorates memory impairments induced by Aβ, we tested the effect of β-amyrin on memory impairments in an Aβ-injected mouse AD model (Fig. 6A).

제안 방법

To induce LTP, two trains of high frequency stimulation (HFS: 100Hz, 100 pulses in 1 s, 30 s interval) were introduced at 20 min after the initiation of a stable baseline. LTP was quantified by comparing the mean fEPSP slope at 80 min after the HFS period with the mean fEPSP slope during the baseline period and calculating the percentage change from the baseline. For the experiments, slices were incubated in ACSF containing vehicle or drugs for 30 min, and then further incubated in ACSF containing Aβ (1 μM) and/or drugs for 2 h before recording.
To test this, we examined the effect of delayed treatment with β-amyrin on established LTP impairment induced by Aβ (Fig. 3A).

대상 데이터

Artificial cerebrospinal fluid (ACSF) was comprised of 124mM NaCl, 3 mM KCl, 26 mM NaHCO₃, 1.25 mM NaH₂PO₄, 2 mM CaCl₂, 1 mM MgSO₄, and 10 mM D-glucose. We rapidly removed the brain and isolated the mouse hippocampus.
Thirty minutes after the habituation; mice were re-placed in the same box with two distinct objects. The objects consisted of a glass box and a plastic cylinder. Mice were allowed to freely explore the objects freely for 10 min.

데이터처리

Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for multiple comparisons and t-test for single comparisons.

후속연구

It could be speculated that β-amyrin may be metabolized in the liver and the metabolite of β-amyrin may act differently in the brain. Further study will be needed to clarify this.

참고문헌 (49)

Amani M Shokouhi G Salari AA 2019 Minocycline prevents the development of depression-like behavior and hippocampal inflammation in a rat model of Alzheimer’s disease Psychopharmacology (Berl.) 236 1281 1292 10.1007/s00213-018-5137-8 30515523

상세보기
Arbel-Ornath M Hudry E Boivin JR Hashimoto T Takeda S Kuchibhotla KV Hou S Lattarulo CR Belcher AM Shakerdge N Trujillo PB Muzikansky A Betensky RA Hyman BT Bacskai BJ 2017 Soluble oligomeric amyloid-beta induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain Mol. Neurodegener 12 27 10.1186/s13024-017-0169-9 28327181

상세보기
Beurel E Grieco SF Jope RS 2015 Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases Pharmacol. Ther 148 114 131 10.1016/j.pharmthera.2014.11.016 25435019

상세보기
Birnbaum JH Bali J Rajendran L Nitsch RM Tackenberg C 2015 Calcium flux-independent NMDA receptor activity is required for Abeta oligomer-induced synaptic loss Cell Death Dis 6 e1791 10.1038/cddis.2015.160 26086964

상세보기
Chen TJ Wang DC Chen SS 2009 Amyloid-beta interrupts the PI3K-Akt-mTOR signaling pathway that could be involved in brain-derived neurotrophic factor-induced Arc expression in rat cortical neurons J. Neurosci. Res 87 2297 2307 10.1002/jnr.22057 19301428

상세보기
Chicca A Marazzi J Gertsch J 2012 The antinociceptive triterpene beta-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting cannabinoid receptors Br. J. Pharmacol 167 1596 1608 10.1111/j.1476-5381.2012.02059.x 22646533

상세보기
da Silva KA Paszcuk AF Passos GF Silva ES Bento AF Meotti FC Calixto JB 2011 Activation of cannabinoid receptors by the pentacyclic triterpene alpha,beta-amyrin inhibits inflammatory and neuropathic persistent pain in mice Pain 152 1872 1887 10.1016/j.pain.2011.04.005 21620566

상세보기
Dubois B Feldman HH Jacova C Dekosky ST Barberger-Gateau P Cummings J Delacourte A Galasko D Gauthier S Jicha G Meguro K O’Brien J Pasquier F Robert P Rossor M Salloway S Stern Y Visser PJ Scheltens P 2007 Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria Lancet Neurol 6 734 746 10.1016/S1474-4422(07)70178-3 17616482

상세보기
Ferretti MT Allard S Partridge V Ducatenzeiler A Cuello AC 2012 Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer’s disease-like amyloid pathology J. Neuroinflammation 9 62 10.1186/1742-2094-9-62 22472085

상세보기
Fu AK Hung KW Huang H Gu S Shen Y Cheng EY Ip FC Huang X Fu WY Ip NY 2014 Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer’s disease Proc. Natl. Acad. Sci. U.S.A 111 9959 9964 10.1073/pnas.1405803111 24958880

상세보기
Gregoire CA Bonenfant D Le Nguyen A Aumont A Fernandes KJ 2014 Untangling the influences of voluntary running, environmental complexity, social housing and stress on adult hippocampal neurogenesis PLoS ONE 9 e86237 10.1371/journal.pone.0086237 24465980

상세보기
Hardy J Selkoe DJ 2002 The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics Science 297 353 356 10.1126/science.1072994 12130773

상세보기
Haughey NJ Nath A Chan SL Borchard AC Rao MS Mattson MP 2002 Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease J. Neurochem 83 1509 1524 10.1046/j.1471-4159.2002.01267.x 12472904

상세보기
Ishii M Nakahara T Ikeuchi S Nishimura M 2015 beta-Amyrin induces angiogenesis in vascular endothelial cells through the Akt/endothelial nitric oxide synthase signaling pathway Biochem. Biophys. Res. Commun 467 676 682 10.1016/j.bbrc.2015.10.085 26498523

상세보기
Jeon SJ Park HJ Gao Q Lee HE Park SJ Hong E Jang DS Shin CY Cheong JH Ryu JH 2015 Positive effects of beta-amyrin on pentobarbital-induced sleep in mice via GABAergic neurotransmitter system Behav. Brain Res 291 232 236 10.1016/j.bbr.2015.05.005 26026786

상세보기
Jiang Y Liu Y Zhu C Ma X Ma L Zhou L Huang Q Cen L Pi R Chen X 2015 Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice Neurobiol. Learn. Mem 121 20 29 10.1016/j.nlm.2015.03.003 25838119

상세보기
Jo J Whitcomb DJ Olsen KM Kerrigan TL Lo SC Bru-Mercier G Dickinson B Scullion S Sheng M Collingridge G Cho K 2011 Abeta(1？42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3beta Nat. Neurosci 14 545 547 10.1038/nn.2785 21441921

상세보기
Kim HY Lee DK Chung BR Kim HV Kim Y 2016 Intracerebroventricular injection of amyloid-beta peptides in normal mice to acutely induce alzheimer-like cognitive deficits J. Vis. Exp 109 e53308
Kitagishi Y Nakanishi A Ogura Y Matsuda S 2014 Dietary regulation of PI3K/AKT/GSK-3beta pathway in Alzheimer’s disease Alzheimers Res. Ther 6 35 10.1186/alzrt265 25031641

상세보기
Krishnan K Mathew LE Vijayalakshmi NR Helen A 2014 Anti-inflammatory potential of beta-amyrin, a triterpenoid isolated from Costus igneus Inflammopharmacology 22 373 385 10.1007/s10787-014-0218-8 25300965

상세보기
Ma J Gao Y Jiang L Chao FL Huang W Zhou CN Tang W Zhang L Huang CX Zhang Y Luo YM Xiao Q Yu HR Jiang R Tang Y 2017 Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer’s disease mice Oncotarget 8 27676 27692 28430602

상세보기
Maurya R Srivastava A Shah P Siddiqi MI Rajendran SM Puri A Yadav PP 2012 beta-Amyrin acetate and beta-amyrin palmitate as antidyslipidemic agents from Wrightia tomen-tosa leaves Phytomedicine 19 682 685 10.1016/j.phymed.2012.03.013 22541636

상세보기
Mu Y Gage FH 2011 Adult hippocampal neurogenesis and its role in Alzheimer’s disease Mol. Neurodegener 6 85 10.1186/1750-1326-6-85 22192775

상세보기
Nabavi S Fox R Proulx CD Lin JY Tsien RY Malinow R 2014 Engineering a memory with LTD and LTP Nature 511 348 352 10.1038/nature13294 24896183

상세보기
Nair AB Jacob S 2016 A simple practice guide for dose conversion between animals and human J. Basic Clin. Pharm 7 27 31 10.4103/0976-0105.177703 27057123

상세보기
Nair SA Sabulal B Radhika J Arunkumar R Subramoniam A 2014 Promising anti-diabetes mellitus activity in rats of beta-amyrin palmitate isolated from Hemidesmus indicus roots Eur. J. Pharmacol 734 77 82 10.1016/j.ejphar.2014.03.050 24726843

상세보기
Noble W Garwood C Stephenson J Kinsey AM Hanger DP Anderton BH 2009 Minocycline reduces the development of abnormal tau species in models of Alzheimer’s disease FASEB J 23 739 750 10.1096/fj.08-113795 19001528

상세보기
Okoye NN Ajaghaku DL Okeke HN Ilodigwe EE Nworu CS Okoye FB 2014 beta-Amyrin and alpha-amyrin acetate isolated from the stem bark of Alstonia boonei display profound anti-inflammatory activity Pharm. Biol 52 1478 1486 10.3109/13880209.2014.898078 25026352

상세보기
Park SJ Ahn YJ Oh SR Lee Y Kwon G Woo H Lee HE Jang DS Jung JW Ryu JH 2014 Amyrin attenuates scopolamine-induced cognitive impairment in mice Biol. Pharm. Bull 37 1207 1213 10.1248/bpb.b14-00113 24989012

상세보기
Penn AC Zhang CL Georges F Royer L Breillat C Hosy E Petersen JD Humeau Y Choquet D 2017 Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors Nature 549 384 388 10.1038/nature23658 28902836

상세보기
Reddy PH 2013 Amyloid beta-induced glycogen synthase kinase 3beta phosphorylated VDAC1 in Alzheimer’s disease: implications for synaptic dysfunction and neuronal damage Biochim. Biophys. Acta 1832 1913 1921 10.1016/j.bbadis.2013.06.012 23816568

상세보기
Rodriguez JJ Jones VC Tabuchi M Allan SM Knight EM LaFerla FM Oddo S Verkhratsky A 2008 Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease PLoS ONE 3 e2935 10.1371/journal.pone.0002935 18698410

상세보기
Rodriguez JJ Noristani HN Olabarria M Fletcher J Somerville TD Yeh CY Verkhratsky A 2011 Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimer’s disease Curr. Alzheimer Res 8 707 717 10.2174/156720511797633214 21453244
Rodriguez JJ Verkhratsky A 2011 Neurogenesis in Alzheimer’s disease J. Anat 219 78 89 10.1111/j.1469-7580.2011.01343.x 21323664

상세보기
Santos FA Frota JT Arruda BR de Melo TS da Silva AA Brito GA Chaves MH Rao VS 2012 Antihyperglycemic and hypolipidemic effects of alpha, beta-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice Lipids Health Dis 11 98 10.1186/1476-511X-11-98 22867128

상세보기
Selkoe DJ 1991 The molecular pathology of Alzheimer’s disease Neuron 6 487 498 10.1016/0896-6273(91)90052-2 1673054

상세보기
Shimshek DR Bus T Schupp B Jensen V Marx V Layer LE Kohr G Sprengel R 2017 Different forms of AMPA receptor mediated LTP and their correlation to the spatial working memory formation Front. Mol. Neurosci 10 214 10.3389/fnmol.2017.00214 28725178

상세보기
Stein ES Itsekson-Hayosh Z Aronovich A Reisner Y Bushi D Pick CG Tanne D Chapman J Vlachos A Maggio N 2015 Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke Sci. Rep 5 7912 10.1038/srep07912 25604482

상세보기
Szakiel A Paczkowski C Pensec F Bertsch C 2012 Fruit cuticular waxes as a source of biologically active triterpenoids Phytochem. Rev 11 263 284 10.1007/s11101-012-9241-9 23519009

상세보기
Tapia-Rojas C Aranguiz F Varela-Nallar L Inestrosa NC 2016 Voluntary running attenuates memory loss, decreases neuropathological changes and induces neurogenesis in a mouse model of Alzheimer’s disease Brain Pathol 26 62 74 10.1111/bpa.12255 25763997

상세보기
Thirupathi A Silveira PC Nesi RT Pinho RA 2017 beta-Amyrin, a pentacyclic triterpene, exhibits anti-fibrotic, anti-inflammatory, and anti-apoptotic effects on dimethyl nitrosamine-induced hepatic fibrosis in male rats Hum. Exp. Toxicol 36 113 122 10.1177/0960327116638727 27009110

상세보기
Tiwari SK Seth B Agarwal S Yadav A Karmakar M Gupta SK Choubey V Sharma A Chaturvedi RK 2015 Ethosuximide induces hippocampal neurogenesis and reverses cognitive deficits in an amyloid-beta toxin-induced alzheimer rat model via the phosphatidylinositol 3-kinase (PI3K)/Akt/Wnt/beta-catenin pathway J. Biol. Chem 290 28540 28558 10.1074/jbc.M115.652586 26420483

상세보기
Tozzi A Sclip A Tantucci M de Iure A Ghiglieri V Costa C Di Filippo M Borsello T Calabresi P 2015 Region- and age-dependent reductions of hippocampal long-term potentiation and NMDA to AMPA ratio in a genetic model of Alzheimer’s disease Neurobiol. Aging 36 123 133 10.1016/j.neurobiolaging.2014.07.002 25104560

상세보기
Viola KL Klein WL 2015 Amyloid beta oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis Acta Neuropathol 129 183 206 10.1007/s00401-015-1386-3 25604547

상세보기
Walsh DM Klyubin I Fadeeva JV Cullen WK Anwyl R Wolfe MS Rowan MJ Selkoe DJ 2002 Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo Nature 416 535 539 10.1038/416535a 11932745

상세보기
Yan R Fan Q Zhou J Vassar R 2016 Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease Neurosci. Biobehav. Rev 65 326 340 10.1016/j.neubiorev.2016.03.025 27044452

상세보기
Yi JH Baek SJ Heo S Park HJ Kwon H Lee S Jung J Park SJ Kim BC Lee YC Ryu JH Kim DH 2018 Direct pharmacological Akt activation rescues Alzheimer’s disease like memory impairments and aberrant synaptic plasticity Neuropharmacology 128 282 292 10.1016/j.neuropharm.2017.10.028 29079294

상세보기
Zhu G Li J He L Wang X Hong X 2015 MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented by memantine through the BDNF-TrkB pathway Br. J. Pharmacol 172 2354 2368 10.1111/bph.13061 25560396

상세보기
Ziabreva I Perry E Perry R Minger SL Ekonomou A Przyborski S Ballard C 2006 Altered neurogenesis in Alzheimer’s disease J. Psychosom. Res 61 311 316 10.1016/j.jpsychores.2006.07.017 16938507

상세보기

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