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研究生:郭玟君
研究生(外文):Wen-Chun Kuo
論文名稱:在MPTP 誘導類帕金森氏症小鼠模式中探討乳酸菌 YM_A 之神經保護功效與機制
論文名稱(外文):The novel neuroprotective effects and mechanism of lactic acid bacteria YM_A in MPTP-induced Parkinson's disease-like mice model
指導教授:蔡英傑蔡英傑引用關係
指導教授(外文):Ying-Chieh Tsai
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:71
中文關鍵詞:帕金森氏症
外文關鍵詞:Parkinson's disease
相關次數:
  • 被引用被引用:1
  • 點閱點閱:332
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  • 收藏至我的研究室書目清單書目收藏:0
帕金森氏症 ( Parkinson’s disease ) 是全球第二常見的神經退化性疾病,患者因為黑質多巴胺神經元退化,導致紋狀體多巴胺總量大幅降低,產生許多行為缺失的問題,包含:靜止時不自主的顫抖、運動遲緩、肌肉僵硬以及姿勢不穩定等等。基於菌腦腸軸線學說研究發現許多精神益生菌可透過菌腦腸軸線影響宿主中樞神經系統的發育和表現。
在本實驗室先前研究發現預先長期給予乳酸菌YM_A的老鼠可以恢復1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP ) 誘導的運動行為缺陷。因此在本研究繼續使用MPTP誘導之類帕金森氏症小鼠模式進一步了解YM_A改善帕金森氏症之功效性與機制,並以爬竿試驗和平衡木試驗評估老鼠行為缺陷改善之能力。因此設計了三種實驗策略欲探討YM_A對中樞神經多巴胺系統的保護功效,分別是事先長期餵食YM_A連續28天並在最後5天進行MPTP注射( pre-treat )、同時餵食乳酸菌和MPTP注射連續19天 ( co-treat ) 以及MPTP注射連續19天期間的後兩週餵食乳酸菌 ( post-treated ) 的實驗流程。
實驗結果發現相較於其他親源相近菌種 ( YM_B以及YM_C ),YM_A改善老鼠行為缺陷的能力皆為最佳,而且餵食YM_A或常用於治療帕金森氏症的藥物L-3,4-dihydroxyphenylalanine ( L-DOPA ) 的老鼠可以增加腦部紋狀體superoxide dismutase ( SOD ) 含量,用以對抗MPTP注射所造成的氧化壓力。此外也發現雖然在給予YM_A並進行MPTP注射的老鼠無法使紋狀體的tyrosine hydroxylase ( TH ) 蛋白質表現量恢復至正常水平,卻可以降低因為MPTP誘導所增加的α-Synuclein蛋白質表現量,使之恢復至正常水平,又α-Synuclein對於神經傳導物質的釋放過程扮演著極為重要的角色,表示YM_A可能透過調節腦部多巴胺之釋放,來達到改善MPTP誘導所產生的行為缺陷問題。
Parkinson’s disease ( PD ) is the second common neurodegenerative diseasecaused by dopaminergic neuron degeneration in substantia nigra pars compacta ( SNpc ) region of brainwhich decreasing dopamine ( DA ) level in straitum. It is also characterized by slowness of movement, muscular rigidity, resting tremor, poor posture, and imbalance. It was discovered that certain psychobiotics strain can influencecentral nerve system ( CNS ) development and function of the host based on microbiome-gut-brain axis ( MGBA ) .
In our previous studies, we founda novel psychobioticsYM_A, which may have potential to improve 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP ) -induced motor deficiencies. In the present study, wecontinue to use MPTP-induced PD-like mice modelandbehavioral test which include pole test and narrow beam test to investigate the ability of YM_A to restoremotor deficiencies. Therefore, we design three experimental strategies which include pre-treat, co-treat, and post-treated modelto explore the neuroprotective effects of YM_A and mechanism.
According to the results of pole test and narrow bean test, YM_A has the best potential to reverse MPTP-induced motor deficiencies comparing toother close relative strains including YM_B and YM_C in three different experimental strategies. And YM_A or L-DOPA treatment can both increase superoxide dismutase ( SOD ) level in striatum to reduce oxidative stress. In addition, it was found that YM_A treatment on MPTP-induced PD-like mice can not rescue tyrosine hydroxylase ( TH ) protein level in striatum, but it can reduce α-Synuclein protein level that was increading by MPTP whichplay an important role in dopamine release in MPTP-induced mice. It represents that YM_A mayimprove MPTP-induced motor deficiency via regulatingdopamine release.
摘要 i
Abstract ii
英文縮寫對照表 iii
目錄 iv
第壹章、緒論 1
第一節、腸道菌相與健康 1
第二節、腸道菌-大腦-腸道 軸線 2
第三節、精神益生菌 4
第四節、帕金森氏症簡介 5
第五節、帕金森氏症之相關研究 6
一、 多巴胺與運動功能之發現 6
二、 帕金森氏症之病理特徵 7
三、 帕金森氏症之病因 7
第六節、帕金森氏症之臨床表現分期 8
第七節、帕金森氏症之治療 9
一、 左旋多巴胺 ( L-DOPA ) 9
二、 多巴胺共同劑 ( Dopamine Agonists ) 10
三、 單胺氧化酶抑制劑 ( MAO-B Inhibitor ) 10
第八節、帕金森氏症之動物模式建立 11
第貳章、實驗動機與目的 12
第參章、實驗材料與方法 13
一、 實驗材料 13
(1)化學藥品 13
(2)試劑套組 14
(3)抗體 14
(4)實驗動物 14
(5)菌種來源 14
二、 儀器設備 15
三、 實驗方法 16
(1)菌種製備 16
(2)MPTP誘導類帕金森氏症小鼠模式建立 17
(3)爬竿試驗 ( Pole Test ) 18
(4)平衡木試驗 ( Narrow Beam Test ) 18
(5)血液採集 19
(6)腦組織取樣 19
(7)腸組織取樣 20
(8)盲腸便收集 20
(9)腦部神經傳導物質多巴胺和正腎上腺素及其代謝物測量 20
(10)腦部SOD ( Superoxide Dismutase ) 含量測量 21
(11)腦部GSH ( Glutathione ) 含量測量 22
(12)腦部紋狀體組織蛋白質萃取 24
(13)蛋白質定量 24
(14)十二烷基硫酸鈉聚丙烯醯胺凝膠電泳 ( SDS-PAGE ) 25
※12%聚丙烯醯胺之分離膠體 ( Separating gel ) 製作 25
※4%聚丙烯醯胺之聚集膠體 ( Stacking gel ) 製作 25
※蛋白質電泳 25
(15)西方墨點法 ( Western Blot ) 26
(16)統計方法 27
第肆章、實驗結果 28
【第一部分】以不同實驗設計流程研究YM_A對MPTP誘導類帕金森氏症小鼠行為缺陷之改善效果 28
一、 比較餵食親源相近菌種對MPTP誘導類帕金森氏症小鼠行為表
現之影響 28
二、 在MPTP長期注射(同時餵食乳酸菌和MPTP注射連續19天)小鼠
模式下比較餵食親源相近菌種對小鼠行為表現之影響 29
三、 在MPTP長期注射(MPTP注射連續19天期間的後兩週餵食乳酸
菌)小鼠模式下比較餵食親源相近菌種對小鼠行為表現之影響
30
【第二部分】探討YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體之影響
及可能參與之機制 31
四、 比較餵食親源相近菌種對MPTP誘導類帕金森氏症小鼠腦部紋
狀體抗氧化物質之影響 32
五、 YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體多巴胺及正腎
上腺素之影響 33
六、 YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體Tyrosine
Hydroxylase蛋白質表現量之影響 33
七、 YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體α-Synuclein
蛋白質表現量之影響 34
第伍章、討論 35
一、YM_A對MPTP誘導類帕金森氏症小鼠行為影響之討論 35
二、YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體氧化壓力與多巴胺
影響及可能參與機制之討論 37
三、YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體α-Synuclein蛋
白質影響及可能參與機制之討論 39
第陸章、結論 41
第柒章、表格與附圖 42
表一、帕金森氏症常用之治療藥物及其副作用 42
圖一、腸道菌-大腦-腸道 軸線示意圖 43
圖二、人類基底核示意圖 44
圖三、帕金森氏症患者腦部變化 45
圖四、帕金森氏症誘導常用藥物之結構 46
圖五、MPTP作用機制 47
圖六、本研究之實驗流程設計示意圖 48
圖七、比較餵食親源相近菌種對MPTP誘導類帕金森氏症小鼠行為表現之
影響 50
圖八、在MPTP長期注射(同時餵食乳酸菌和MPTP注射連續19天)小鼠模
式下比較餵食親源相近菌種對小鼠行為表現之影響 52
圖九、在MPTP長期注射(MPTP注射連續19天期間的後兩週餵食乳酸菌)
小鼠模式下比較餵食親源相近菌種對小鼠行為表現之影響 54
圖十、比較餵食親源相近菌種對MPTP誘導類帕金森氏症小鼠腦部紋狀體
抗氧化物質之影響 56
圖十一、YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體多巴胺及正腎上
腺素之影響 58
圖十二、YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體Tyrosine
Hydroxylase蛋白質表現量之影響 59
圖十三、YM_A對MPTP誘導類帕金森氏症小鼠腦部紋狀體α-Synuclein蛋
白質表現量之影響 60
第捌章、參考文獻 61
1.Butel M-J. Probiotics, gut microbiota and health.
Médecine et maladies infectieuses. 2014;44(1):1-8.
2.Ley RE, Peterson DA, Gordon JI. Ecological and
evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124(4):837-48.
3.Vyas U, Ranganathan N. Probiotics, prebiotics, and
synbiotics: gut and beyond. Gastroenterology Research and Practice.2012.
4.Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ,
Samuel BS, et al. Metagenomic analysis of the human
distal gut microbiome. science. 2006;312(5778):1355-9.
5.Yelshyna D, Gago MF, Bicho E, Fernandes V, Gago NF,
Costa L, et al. Compensatory postural adjustments in
Parkinson’s disease assessed via a virtual reality
environment. Behavioural brain research. 2016;296:384-
92.
6.Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh
C, et al. A human gut microbial gene catalogue
established by metagenomic sequencing. nature.
2010;464(7285):59-65.
7.Principi N, Esposito S. Gut microbiota and central
nervous system development. Journal of Infection.
2016;73(6):536-46.
8.Burokas A, Moloney RD, Dinan TG, Cryan JF. Chapter one-
microbiota regulation of the mammalian gut–brain axis.
Advances in applied microbiology. 2015;91:1-62.
9.Gershon MD. The enteric nervous system: a second brain.
Hospital Practice. 1999;34(7):31-52.
10.Carabotti M, Scirocco A, Maselli MA, Severi C. The
gut-brain axis: interactions between enteric
microbiota, central and enteric nervous systems.
Annals of gastroenterology: quarterly publication of
the Hellenic Society of Gastroenterology.
2015;28(2):203.
11.Moloney RD, Desbonnet L, Clarke G, Dinan TG, Cryan JF.
The microbiome: stress, health and disease. Mammalian
genome. 2014;25(1-2):49-74.
12.Collins SM, Surette M, Bercik P. The interplay between
the intestinal microbiota and the brain. Nature
Reviews Microbiology. 2012;10(11):735-42.
13.Grenham S, Clarke G, Cryan JF, Dinan TG. Brain–gut–
microbe communication in health and disease. Frontiers
in physiology. 2011;2:94.
14.Cersosimo MG, Benarroch EE. Neural control of the
gastrointestinal tract: implications for Parkinson
disease. Movement Disorders. 2008;23(8):1065-75.
15.Foster JA, Neufeld K-AM. Gut–brain axis: how the
microbiome influences anxiety and depression. Trends
in neurosciences. 2013;36(5):305-12.
16.Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF,
Burnet PW. Psychobiotics and the manipulation of
bacteria–gut–brain signals. Trends in neurosciences.
2016;39(11):763-81.
17.Thayer JF, Sternberg EM. Neural concomitants of
immunity—Focus on the vagus nerve. Neuroimage.
2009;47(3):908.
18.de Haan JJ, Hadfoune Mh, Lubbers T, Hodin C, Lenaerts
K, Ito A, et al. Lipid-rich enteral nutrition
regulates mucosal mast cell activation via the vagal
anti-inflammatory reflex. American Journal of
Physiology-Gastrointestinal and Liver Physiology.
2013;305(5):G383-G91.
19.Mezzacappa ES, Kelsey RM, Katkin ES, Sloan RP. Vagal
rebound and recovery from psychological stress.
Psychosomatic medicine. 2001;63(4):650-7.
20.Spalding TW, Jeffers LS, Porges SW, Hatfield BD. Vagal
and cardiac reactivity to psychological stressors in
trained and untrained men. Medicine & Science in
Sports & Exercise. 2000.
21.Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina
GI, Watkins LR, et al. Vagus nerve stimulation
attenuates the systemic inflammatory response to
endotoxin. Nature. 2000;405(6785):458-62.
22.Ghia JE, Blennerhassett P, Kumar–Ondiveeran H, Verdu
EF, Collins SM. The vagus nerve: a tonic inhibitory
influence associated with inflammatory bowel disease
in a murine model. Gastroenterology. 2006;131(4):1122-
30.
23.Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac
HM, Dinan TG, et al. Ingestion of Lactobacillus strain
regulates emotional behavior and central GABA receptor
expression in a mouse via the vagus nerve. Proceedings
of the National Academy of Sciences.
2011;108(38):16050-5.
24.Bercik P, Park A, Sinclair D, Khoshdel A, Lu J, Huang
X, et al. The anxiolytic effect of Bifidobacterium
longum NCC3001 involves vagal pathways for gut–brain
communication. Neurogastroenterology & Motility.
2011;23(12):1132-9.
25.De Lartigue G, de La Serre CB, Raybould HE. Vagal
afferent neurons in high fat diet-induced obesity;
intestinal microflora, gut inflammation and
cholecystokinin. Physiology & behavior.
2011;105(1):100-5.
26.Horn T, Klein J. Neuroprotective effects of lactate in
brain ischemia: dependence on anesthetic drugs.
Neurochemistry international. 2013;62(3):251-7.
27.Moretti M, Valvassori SS, Varela RB, Ferreira CL,
Rochi N, Benedet J, et al. Behavioral and
neurochemical effects of sodium butyrate in an animal
model of mania. Behavioural pharmacology.
2011;22(8):766-72.
28.Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M,
et al. Butyrate improves insulin sensitivity and
increases energy expenditure in mice. Diabetes.
2009;58(7):1509-17.
29.Fushimi T, Suruga K, Oshima Y, Fukiharu M, Tsukamoto
Y, Goda T. Dietary acetic acid reduces serum
cholesterol and triacylglycerols in rats fed a
cholesterol-rich diet. British Journal of Nutrition.
2006;95(05):916-24.
30.Demigné C, Morand C, Levrat M-A, Besson C, Moundras C,
Rémésy C. Effect of propionate on fatty acid and
cholesterol synthesis and on acetate metabolism in
isolated rat hepatocytes. British Journal of
Nutrition. 1995;74(02):209-19.
31.Todesco T, Rao AV, Bosello O, Jenkins D. Propionate
lowers blood glucose and alters lipid metabolism in
healthy subjects. The American journal of clinical
nutrition. 1991;54(5):860-5.
32.Bergman E. Energy contributions of volatile fatty
acids from the gastrointestinal tract in various
species. Physiological reviews. 1990;70(2):567-90.
33.Macpherson AJ, Slack E. The functional interactions of
commensal bacteria with intestinal secretory IgA.
Current opinion in gastroenterology. 2007;23(6):673-8.
34.Hakansson A, Molin G. Gut microbiota and inflammation.
Nutrients. 2011;3(6):637-82.
35.Joint F. WHO Expert consultation on evaluation of
health and nutritional properties of probiotics in
food including powder milk with live lactic acid
bacteria. Córdoba, Argentina October. 2001:1-4.
36.Group JFWW, Group JFWW. Guidelines for the evaluation
of probiotics in food. London: World Health
Organization, ON, Canada: Food and Agriculture
Organization. 2002.
37.Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel
class of psychotropic. Biological psychiatry.
2013;74(10):720-6.
38.Oleskin AV, Shenderov BA. Neuromodulatory effects and
targets of the SCFAs and gasotransmitters produced by
the human symbiotic microbiota. Microbial ecology in
health and disease. 2016;27(1):30971.
39.Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan J,
Dinan T. Effects of the probiotic Bifidobacterium
infantis in the maternal separation model of
depression. Neuroscience. 2010;170(4):1179-88.
40.Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER,
McCue T, et al. Microbiota modulate behavioral and
physiological abnormalities associated with
neurodevelopmental disorders. Cell. 2013;155(7):1451-
63.
41.Rai SN, Yadav SK, Singh D, Singh SP. Ursolic acid
attenuates oxidative stress in nigrostriatal tissue
and improves neurobehavioral activity in MPTP-induced
Parkinsonian mouse model. J Chem Neuroanat.
2016;71:41-9.
42.De Lau LM, Breteler MM. Epidemiology of Parkinson's
disease. The Lancet Neurology. 2006;5(6):525-35.
43.Dauer W, Przedborski S. Parkinson's disease:
mechanisms and models. Neuron. 2003;39(6):889-909.
44.Schapira AH. Mitochondria in the aetiology and
pathogenesis of Parkinson's disease. The Lancet
Neurology. 2008;7(1):97-109.
45.Sveinbjornsdottir S. The clinical symptoms of
Parkinson's disease. Journal of Neurochemistry.
2016;139(S1):318-24.
46.Rajput A. Frequency and cause of Parkinson’s disease.
Canadian Journal of Neurological Sciences/Journal
Canadien des Sciences Neurologiques. 1992;19(S1):103-
7.
47.De Rijk M, Launer L, Berger K, Breteler M, Dartigues
J, Baldereschi M, et al. Prevalence of Parkinson's
disease in Europe: A collaborative study of.
Neurology. 2000;54(5):S21-S3.
48.Golbe LI. Young‐onset Parkinson's disease A clinical
review. Neurology. 1991;41(2 Part 1):168-168.
49.Samii A, Nutt JG, Ransom BR. Parkinson's disease.
Lancet (London, England). 2004; 363: 1783-93
50.Parkinson J. An essay on the shaking palsy. The
Journal of neuropsychiatry and clinical neurosciences.
2002;14(2):223-36.
51.Davie CA. A review of Parkinson's disease. British
medical bulletin. 2008;86(1):109-27.
52.Yeragani VK, Tancer M, Chokka P, Baker GB. Arvid
Carlsson, and the story of dopamine. Indian journal of
psychiatry. 2010;52(1):87.
53.Carlsson A, Lindqvist M, Magnusson T. 3, 4-
Dihydroxyphenylalanine and 5-hydroxytryptophan as
reserpine antagonists. 1957.
54.Abbott A. Neuroscience: The molecular wake-up call.
Nature. 2007;447(7143):368-70.
55.Carlsson A. Thirty years of dopamine research.
Advances in neurology. 1993;60:1-10.
56.Carlsson A. Basic concepts underlying recent
developments in the field of Parkinson's disease.
Contemporary neurology series. 1971;8:1.
57.Carlsson A. Speculations on the control of mental and
motor functions by dopamine-modulated cortico-striato-
thalamo-cortical feedback loops. The Mount Sinai
journal of medicine, New York. 1988;55(1):6-10.
58.Fearnley JM, Lees AJ. Ageing and Parkinson's disease:
substantia nigra regional selectivity. Brain.
1991;114(5):2283-301.
59.Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ,
Jakes R, Goedert M. α-Synuclein in Lewy bodies.
Nature. 1997;388(6645):839-40.
60.Braak H, Del Tredici K, Rüb U, de Vos RA, Steur ENJ,
Braak E. Staging of brain pathology related to
sporadic Parkinson’s disease. Neurobiology of aging.
2003;24(2):197-211.
61.Wakabayashi K, Takahashi H. Neuropathology of
autonomic nervous system in Parkinson's disease.
European neurology. 1997;38(Suppl. 2):2-7.
62.Blesa J, Phani S, Jackson-Lewis V, Przedborski S.
Classic and new animal models of Parkinson's disease.
BioMed Research International. 2012.
63.Parker WD, Parks JK, Swerdlow RH. Complex I deficiency
in Parkinson's disease frontal cortex. Brain research.
2008;1189:215-8.
64.Jenner P. Oxidative stress in Parkinson's disease.
Annals of neurology. 2003;53(S3):S26-S38.
65.Dinis-Oliveira R, Remiao F, Carmo H, Duarte J, Navarro
AS, Bastos M, et al. Paraquat exposure as an
etiological factor of Parkinson's disease.
Neurotoxicology. 2006;27(6):1110-22.
66.Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia
A, Dutra A, et al. Mutation in the α-synuclein gene
identified in families with Parkinson's disease.
science. 1997;276(5321):2045-7.
67.Bostantjopoulou S, Katsarou Z, Papadimitriou A,
Veletza V, Hatzigeorgiou G, Lees A. Clinical features
of parkinsonian patients with the α‐synuclein (G209A)
mutation. Movement disorders. 2001;16(6):1007-13.
68.Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M,
Kösel S, et al. AlaSOPro mutation in the gene encoding
α-synuclein in Parkinson's disease. Nature genetics.
1998;18(2):106-8.
69.Abbas N, Lücking CB, Ricard S, Dürr A, Bonifati V, De
Michele G, et al. A wide variety of mutations in the
parkin gene are responsible for autosomal recessive
parkinsonism in Europe. Human molecular genetics.
1999;8(4):567-74.
70.Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura
Y, Minoshima S, et al. Mutations in the parkin gene
cause autosomal recessive juvenile parkinsonism.
Nature. 1998;392(6676):605-8.
71.Lücking CB, Dürr A, Bonifati V, Vaughan J, De Michele
G, Gasser T, et al. Association between early-onset
Parkinson's disease and mutations in the parkin gene.
New England Journal of Medicine. 2000;342(21):1560-7.
72.Pramstaller PP, Schlossmacher MG, Jacques TS,
Scaravilli F, Eskelson C, Pepivani I, et al. Lewy body
Parkinson's disease in a large pedigree with 77 Parkin
mutation carriers. Annals of neurology.
2005;58(3):411-22.
73.Shimura H, Hattori N, Kubo S-i, Mizuno Y, Asakawa S,
Minoshima S, et al. Familial Parkinson disease gene
product, parkin, is a ubiquitin-protein ligase. Nature
genetics. 2000;25(3):302-5.
74.Shimura H, Schlossmacher MG, Hattori N, Frosch MP,
Trockenbacher A, Schneider R, et al. Ubiquitination of
a new form of α-synuclein by parkin from human brain:
implications for Parkinson's disease. Science.
2001;293(5528):263-9.
75.Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E,
et al. The ubiquitin pathway in Parkinson's disease.
Nature. 1998;395(6701):451-2.
76.Gasser T. Overview of the genetics of parkinsonism.
Advances in neurology. 2003;91:143.
77.Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM,
Harvey K, Gispert S, et al. Hereditary early-onset
Parkinson's disease caused by mutations in PINK1.
Science. 2004;304(5674):1158-60.
78.Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE,
Caputo V, et al. PINK1 mutations are associated with
sporadic early‐onset parkinsonism. Annals of
neurology. 2004;56(3):336-41.
79.Hatano Y, Li Y, Sato K, Asakawa S, Yamamura Y,
Tomiyama H, et al. Novel PINK1 mutations in early‐
onset parkinsonism. Annals of neurology.
2004;56(3):424-7.
80.Van Duijn C, Dekker M, Bonifati V, Galjaard R,
Houwing-Duistermaat J, Snijders P, et al. Park7, a
novel locus for autosomal recessive early-onset
parkinsonism, on chromosome 1p36. The American Journal
of Human Genetics. 2001;69(3):629-34.
81.Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld
GJ, Krieger E, et al. Mutations in the DJ-1 gene
associated with autosomal recessive early-onset
parkinsonism. Science. 2003;299(5604):256-9.
82.Xu J, Zhong N, Wang H, Elias JE, Kim CY, Woldman I, et
al. The Parkinson's disease-associated DJ-1 protein is
a transcriptional co-activator that protects against
neuronal apoptosis. Human molecular genetics.
2005;14(9):1231-41.
83.Shendelman S, Jonason A, Martinat C, Leete T,
Abeliovich A. DJ-1 is a redox-dependent molecular
chaperone that inhibits α-synuclein aggregate
formation. PLoS Biol. 2004;2(11):e362.
84.West A, Periquet M, Lincoln S, Lücking CB, Nicholl D,
Bonifati V, et al. Complex relationship between Parkin
mutations and Parkinson disease. American journal of
medical genetics. 2002;114(5):584-91.
85.Singer TP, Ramsay RR. Mechanism of the neurotoxicity
of MPTP: an update. FEBS letters. 1990;274(1-2):1-8.
86.Samii A, Calne DB. Research into the etiology of
Parkinson’s disease. Parkinson disease, London, Martin
Dunitz. 1999:229-36.
87.Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS.
Environmental risk factors and Parkinson's disease: a
metaanalysis. Environmental research. 2001;86(2):122-
7.
88.Nistico R, Mehdawy B, Piccirilli S, Mercuri N.
Paraquat-and rotenone-induced models of Parkinson's
disease. SAGE Publications; 2011.
89.Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson
JR, Kim JH, et al. Mechanism of toxicity in rotenone
models of Parkinson's disease. Journal of
Neuroscience. 2003;23(34):10756-64.
90.Hoehn MM, Yahr MD. Parkinsonism onset, progression,
and mortality. Neurology. 1967;17(5):427-427.
91.Schapira A. Progress in Parkinson’s disease. European
journal of neurology. 2008;15(1):5-13.
92.Connolly BS, Lang AE. Pharmacological treatment of
Parkinson disease: a review. Jama. 2014;311(16):1670-
83.
93.Hauser RA, McDermott MP, Messing S. Factors associated
with the development of motor fluctuations and
dyskinesias in Parkinson disease. Archives of
neurology. 2006;63(12):1756-60.
94.Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y,
Evans A, Lees A, et al. Fourteen-year final report of
the randomized PDRG-UK trial comparing three initial
treatments in PD. Neurology. 2008;71(7):474-80.
95.Hauser RA, Rascol O, Korczyn AD, Jon Stoessl A, Watts
RL, Poewe W, et al. Ten‐year follow‐up of Parkinson's
disease patients randomized to initial therapy with
ropinirole or levodopa. Movement Disorders.
2007;22(16):2409-17.
96.Investigators PSGCC. Long-term effect of initiating
pramipexole vs levodopa in early Parkinson disease.
Archives of Neurology. 2009;66(5):563.
97.Fernandez HH, Chen JJ. Monoamine Oxidase‐B Inhibition
in the Treatment of Parkinson's Disease.
Pharmacotherapy: The journal of human pharmacology and
drug therapy. 2007;27(12P2):174S-85S.
98.Pahwa R, Factor S, Lyons K, Ondo W, Gronseth G,
Bronte-Stewart H, et al. Practice parameter: treatment
of Parkinson disease with motor fluctuations and
dyskinesia (an evidence-based review) Report of the
Quality Standards Subcommittee of the American Academy
of Neurology. Neurology. 2006;66(7):983-95.
99.Przedborski S, Vila M. MPTP: a review of its
mechanisms of neurotoxicity. Clinical Neuroscience
Research. 2001;1(6):407-18.
100.Przedborski S, Vila M. The 1‐Methyl‐4‐Phenyl‐1, 2, 3,
6‐Tetrahydropyridine Mouse Model. Annals of the New
York Academy of Sciences. 2003;991(1):189-98.
101.Luchtman DW, Shao D, Song C. Behavior,
neurotransmitters and inflammation in three regimens
of the MPTP mouse model of Parkinson's disease.
Physiology & behavior. 2009;98(1):130-8.
102.Matsuura K, Kabuto H, Makino H, Ogawa N. Pole test is
a useful method for evaluating the mouse movement
disorder caused by striatal dopamine depletion.
Journal of neuroscience methods. 1997;73(1):45-8.
103.Ogawa N, Hirose Y, Ohara S, Ono T, Watanabe Y. A
simple quantitative bradykinesia test in MPTP-treated
mice. Research communications in chemical pathology
and pharmacology. 1985;50(3):435-41.
104.Quinn LP, Perren MJ, Brackenborough KT, Woodhams PL,
Vidgeon-Hart M, Chapman H, et al. A beam-walking
apparatus to assess behavioural impairments in MPTP-
treated mice: pharmacological validation with R-(−)-
deprenyl. Journal of neuroscience methods.
2007;164(1):43-9.
105.Delaville C, De Deurwaerdère P, Benazzouz A.
Noradrenaline and Parkinson's disease. Frontiers in
systems neuroscience. 2011;5.
106.Cash R, Dennis T, L'Heureux R, Raisman R, Javoy-Agid
F, Scatton B. Parkinson's disease and dementia
Norepinephrine and dopamine in locus ceruleus.
Neurology. 1987;37(1):42-42.
107.Gesi M, Soldani P, Giorgi F, Santinami A, Bonaccorsi
I, Fornai F. The role of the locus coeruleus in the
development of Parkinson's disease. Neuroscience &
Biobehavioral Reviews. 2000;24(6):655-68.
108.Marien MR, Colpaert FC, Rosenquist AC. Noradrenergic
mechanisms in neurodegenerative diseases: a theory.
Brain Research Reviews. 2004;45(1):38-78.
109. Fornai F, di Poggio AB, Pellegrini A,
Ruggieri S, Paparelli A. Noradrenaline in Parkinson's
disease: from disease progression to current
therapeutics. Current medicinal chemistry.
2007;14(22):2330-4.
110.Venda LL, Cragg SJ, Buchman VL, Wade-Martins R. α-
Synuclein and dopamine at the crossroads of
Parkinson's disease. Trends in neurosciences.
2010;33(12):559-68.
111.Jankovic J. Parkinson’s disease: clinical features
and diagnosis. Journal of Neurology, Neurosurgery &
Psychiatry. 2008;79(4):368-76.
112.Hartmann A. Postmortem studies in Parkinson's
disease. Dialogues in clinical neuroscience.
2004;6(3):281.
113.Hastings TG. The role of dopamine oxidation in
mitochondrial dysfunction: implications for
Parkinson’s disease. Journal of bioenergetics and
biomembranes. 2009;41(6):469-72.
114.Lee D-H, Kim C-S, Lee YJ. Astaxanthin protects
against MPTP/MPP+-induced mitochondrial dysfunction
and ROS production in vivo and in vitro. Food and
chemical toxicology. 2011;49(1):271-80.
115.Hauser DN, Hastings TG. Mitochondrial dysfunction and
oxidative stress in Parkinson's disease and monogenic
parkinsonism. Neurobiology of disease. 2013;51:35-42.
116.Subramaniam SR, Chesselet M-F. Mitochondrial
dysfunction and oxidative stress in Parkinson's
disease. Progress in neurobiology. 2013;106:17-32.
117.Zhou C, Huang Y, Przedborski S. Oxidative stress in
Parkinson's disease. Annals of the new York Academy
of Sciences. 2008;1147(1):93-104.
118.Machado A, Herrera A, Venero J, Santiago M, De Pablos
R, Villarán R, et al. Inflammatory animal model for
Parkinson's disease: the intranigral injection of LPS
induced the inflammatory process along with the
selective degeneration of nigrostriatal dopaminergic
neurons. ISRN neurology. 2011;2011.
119.Hunter RL, Dragicevic N, Seifert K, Choi DY, Liu M,
Kim HC, et al. Inflammation induces mitochondrial
dysfunction and dopaminergic neurodegeneration in the
nigrostriatal system. Journal of neurochemistry.
2007;100(5):1375-86.
120.Sanchez-Guajardo V, Tentillier N, Romero-Ramos M. The
relation between α-synuclein and microglia in
Parkinson’s disease: Recent developments.
Neuroscience. 2015;302:47-58.
121.Zhang Q-S, Heng Y, Yuan Y-H, Chen N-H. Pathological
α-synuclein exacerbates the progression of
Parkinson’s disease through microglial activation.
Toxicology letters. 2017;265:30-7.
122.Blum-Degena D, Müller T, Kuhn W, Gerlach M, Przuntek
H, Riederer P. Interleukin-1β and interleukin-6 are
elevated in the cerebrospinal fluid of Alzheimer's
and de novo Parkinson's disease patients.
Neuroscience letters. 1995;202(1):17-20.
123.Mogi M, Harada M, Riederer P, Narabayashi H, Fujita
K, Nagatsu T. Tumor necrosis factor-α (TNF-α)
increases both in the brain and in the cerebrospinal
fluid from parkinsonian patients. Neuroscience
letters. 1994;165(1):208-10.
124.Prajapati P, Sripada L, Singh K, Bhatelia K, Singh R,
Singh R. TNF-α regulates miRNA targeting
mitochondrial complex-I and induces cell death in
dopaminergic cells. Biochimica et Biophysica Acta
(BBA)-Molecular Basis of Disease. 2015;1852(3):451-
61.
125.Vivekanantham S, Shah S, Dewji R, Dewji A, Khatri C,
Ologunde R. Neuroinflammation in Parkinson's disease:
role in neurodegeneration and tissue repair.
International Journal of Neuroscience.
2015;125(10):717-25.
126.Barcia C, Bahillo AS, Fernández‐Villalba E, Bautista
V, Poza PY, Fernández‐Barreiro A, et al. Evidence of
active microglia in substantia nigra pars compacta of
parkinsonian monkeys 1 year after MPTP exposure.
Glia. 2004;46(4):402-9.
127.McGeer PL, McGeer EG. Glial reactions in Parkinson's
disease. Movement Disorders. 2008;23(4):474-83.
128. Imamura K, Hishikawa N, Sawada M, Nagatsu
T, Yoshida M, Hashizume Y. Distribution of major
histocompatibility complex class II-positive
microglia and cytokine profile of Parkinson's disease
brains. Acta neuropathologica. 2003;106(6):518-26.
129.Liu Y-W, Liu W-H, Wu C-C, Juan Y-C, Wu Y-C, Tsai H-P,
et al. Psychotropic effects of Lactobacillus
plantarum PS128 in early life-stressed and naïve
adult mice. Brain research. 2016;1631:1-12.
130.Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, De
Silva HR, et al. The precursor protein of non-Aβ
component of Alzheimer's disease amyloid is a
presynaptic protein of the central nervous system.
Neuron. 1995;14(2):467-75.
131.Kahle PJ, Neumann M, Ozmen L, Müller V, Jacobsen H,
Schindzielorz A, et al. Subcellular localization of
wild-type and Parkinson's disease-associated mutant
α-synuclein in human and transgenic mouse brain.
Journal of Neuroscience. 2000;20(17):6365-73.
132.Davidson WS, Jonas A, Clayton DF, George JM.
Stabilization of α-synuclein secondary structure upon
binding to synthetic membranes. Journal of Biological
Chemistry. 1998;273(16):9443-9.
133.Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton
MR, Südhof TC. α-Synuclein promotes SNARE-complex
assembly in vivo and in vitro. Science.
2010;329(5999):1663-7.
134.Chandra S, Gallardo G, Fernandez-Chacon R, Schluter
OM, Sudhof TC. Alpha-synuclein cooperates with
CSPalpha in preventing neurodegeneration. Cell.
2005;123(3):383-96.
135.Choi B-K, Choi M-G, Kim J-Y, Yang Y, Lai Y, Kweon D-
H, et al. Large α-synuclein oligomers inhibit
neuronal SNARE-mediated vesicle docking. Proceedings
of the National Academy of Sciences.
2013;110(10):4087-92.
136.Wang L, Das U, Scott DA, Tang Y, McLean PJ, Roy S. α-
synuclein multimers cluster synaptic vesicles and
attenuate recycling. Current Biology.
2014;24(19):2319-26.
137.Scott D, Roy S. α-Synuclein inhibits intersynaptic
vesicle mobility and maintains recycling-pool
homeostasis. Journal of Neuroscience.
2012;32(30):10129-35.
138.Janezic S, Threlfell S, Dodson PD, Dowie MJ, Taylor
TN, Potgieter D, et al. Deficits in dopaminergic
transmission precede neuron loss and dysfunction in a
new Parkinson model. Proceedings of the National
Academy of Sciences. 2013;110(42):E4016-E25.
139.Mosharov EV, Larsen KE, Kanter E, Phillips KA, Wilson
K, Schmitz Y, et al. Interplay between cytosolic
dopamine, calcium, and α-synuclein causes selective
death of substantia nigra neurons. Neuron.
2009;62(2):218-29.
140.Abeliovich A, Schmitz Y, Fariñas I, Choi-Lundberg D,
Ho W-H, Castillo PE, et al. Mice lacking α-synuclein
display functional deficits in the nigrostriatal
dopamine system. Neuron. 2000;25(1):239-52.
141.Lovinger DM, Alvarez VA. Alcohol and basal ganglia
circuitry: Animal models. Neuropharmacology. 2017.
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