مقایسه ارزیابی موفقیت پیوند سلولی در پارکینسون تجربی با سنجش هموسیستئین با علایم رفتاری
DOI::
https://doi.org/10.22100/jkh.v11i4.1535کلمات کلیدی:
هموسیستئین، پارکینسون، 6-هیدروکسی دپامین، پیوند سلولیچکیده
مقدمه: پارکینسون از بیماریهای تخریبی مغز بهشمار میرود. شواهد نشان میدهد که میزان هموسیستئین سرم در بیماری پارکینسون افزایش مییابد. در این مطالعه ارزیابی موفقیت پیوند سلولی با مقایسه سطح سرمی هموسیستئین و علایم رفتاری در پارکینسون تجربی القا شده با 6-هیدروکسی دپامین مورد بررسی قرار گرفت.
مواد و روشها: اين مطالعه تجربی در سال 1393 بر روی موشهای صحرایی نر ویستار انجام شد. موشها ابتدا تحت جراحي استرئوتاکسيک با تزریق 6-هیدروکسی دپامین به ناحیه دسته مغز جلویی میانی نیمکره راست پارکینسونی شده که با آزمون چرخش القاء شده با آپومورفین تأیید گردید. پس از آن موشها تحت درمان با پیوند سلولهای بنیادی قرار گرفته و اثر درمان بر این چرخشها مجدداً بررسی شد. سطح کلی هموسیستئین قبل و شش هفته پس از تزریق 6 -هیدروکسی دپامین و ده هفته پس از پیوند سلولی اندازهگیری گردید. دادهها با آزمونهای آماري تی زوجی و واریانس یک طرفه و توکی تحلیل شدند.
نتايج: سطح کلی هموسیستئین در موشهای پارکینسونی با شمار چرخش بالا، تغییر معنیداری نداشت. ولی ده هفته بعد از پیوند سلولی، سطح کلی هموسیستئین به میزان قابل ملاحظهای کاهش یافت.
نتیجهگیری: از آنجایی که ارتباط مستقیمی بین شدت چرخشهای القاء شده با آپومرفین با درجه آسیب سلولی در هسته جسم سیاه وجود دارد، نتایج ما نشان ميدهند که مقادیر بالاتر هموسیستئین ميتواند نشاندهنده آسیب نورونی بیشتر در این هسته باشد.
مراجع
Fernandez HH. Updates in the medical management of Parkinson disease. Cleve Clin J Med 2012;79:28-35. doi: 10.3949/ccjm.78gr.11005
Uitti RJ. Treatment of Parkinson’s disease: focus on quality of life issues. Parkinsonism Relat Disord 2012;18:S34-6. doi: 10.1016/S1353-8020(11)70013-X
Hu XW, Qin SM, Li D, Hu LF, Liu CF. Elevated homocysteine levels in levodopa-treated idiopathic Parkinson's disease: a meta-analysis. Acta Neurol Scand 2013; 128:73-82. doi: 10.1111/ane.12106
Song IU, Kim JS, Park IS, Kim YD, Cho HJ, Chung SW, Lee KS. Clinical significance of homocysteine (hcy) on dementia in Parkinson's disease. Arch Gerontol Geriatr 2013;57:288-91. doi: 10.1016/j.archger.2013.04.015
O’ Suilleabhain PE, Sung V, Hernandez C, Laccritz L, Dewey RB J, Bottiglieri T, et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 2004;61:865-8. doi: 10.1001/archneur.61.6.865
Tan C, Peng W, Deng Y. Risk factors and predictive factors of cognitive deterioration in patients of vascular cognitive impairment no dementia with subcortical ischemic vascular disease. Zhonghua Yi Xue Za Zhi 2014;94:352-5
Prins ND, Den Heijer T, Hofman A, Koudstaal PJ, Jolles J, Clarke R, et al. Homocysteine and cognitive function in the elderly: the rotterdam scan study. Neurology 2002;59:1375-80.
Quadri P, Fragiacomo C, Pezzati R, Zanda E, Tettamanti M, Lucca U. Homocysteine and B vitamins in mild cognitive impairment and dementia. Clin Chem Lab Med 2005;43:1096-100.
Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and alzheimer’s disease. N Engl J Med 2002;346:476-83. doi: 10.1056/NEJMoa011613
Edney LC, Burns NR, Danthiir V. Subjective well-being in older adults: folate and vitamin B12 independently predict positive affect. Br J Nutr 2015;114:1321-8. doi: 10.1017/S0007114515002949
Korutla L, Furlong HA, Mackler SA. NAC1, A POZ/BTB protein interacts with Parkin and may contribute to Parkinson's disease. Neuroscience 2014;257:86-95.
Yasui K, Kowa H, Nakaso K, Takeshima T, Nakashima K. Plasma homocysteine and MTHFR C677T genotype in levodopa treated patients with PD. Neurology 2001;55:437-40. doi: 10.1212/WNL.55.3.437
dos Santos EF, Busanello EN, Miglioranza A, Zanatta A, Barchak AG, Vargas CR, et al. Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson's disease. Metab Brain Dis 2009;24:257-69. doi: 10.1007/s11011-009-9139-4
Duan W, Ladenheim B, Cutler RG, Kruman II, Cadet JL, Mattson MP. Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson’s disease. J Neurochem 2002;80:101-10.
Sachdev PS, Valenzuela M, Wang XL, Looi JC, Brodaty H. Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals. Neurology 2002;58:1539-41.
Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 2006;580:2994-3005. doi: 10.1016/j.febslet.2006.04.088
Xing H, Peng H, Xuebing C, Sun S. Effect and mechanism of homocysteine on Parkinson’s disease induced by 6-OHDA. Journal of Nanjing Medical University 2008;22:12-7.
Miller JW, Shukitt-Hale B, Villalobos-Molina R, Nadeau MR, Selhub J, Joseph JA. Effect of L-DOPA and the catechol-O-methyltransferase inhibitor Ro 41-0960 on sulfur amino acid metabolites in rats. Clin Neuropharmacol 1997;20:55-66.
Rogers JD, Sanchez-Saffon A, Frol AB, Diaz-Arrastia R. Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. Arch Neurol 2003;60:59-64.
Religa D, Czyzewski K, Styczynska M, Peplonska B, Lokk J, Chodakowska-Zebrowska M, et al. Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in patients with Parkinson’s disease. Neurosci Lett 2006;404:56-60.
Zoccolella S, Lamberti P, Armenise E, de Mari M, Lamberti SV, Mastronardi R, et al. Plasma homocysteine levels in Parkinson's disease: role of antiparkinsonian medications. Parkinsonism Relat Disord 2005;11:131-3. doi: 10.1016/j.parkreldis.2004.07.008
Siniscalchi A, Gallelli L, Mercuri NB, Ibbadu GF, Sarro G. Role of lifestyle factors on plasma homocysteine levels in Pakinson’s disease patients treated with levodopa. Nutr Neuosci 2006;9:11-6. doi: 10.1080/10284150600583446
Kumar R, Agarwal ML, Seth PK. Free radical-generated neurotoxicity of 6-hydroxydopamine. J Neurochem 1995; 64:1703-7.
Soto-Otero R, Mendez-Alvarez E, Hermida-Ameijeiras A, Munoz-Patino AM, Labendeira-Garcia JL. Autooxidation and neurotoxicity of 6-hydroxydopamine in the presence of some antioxidants: potential implication in relation to the pathogenesis of Parkinson’s disease. J Neurochem 2000;74:1605-12.
Ba XH. Therapeutic effects of GM1 on Parkinson's disease in rats and its mechanism. Int J Neurosci 2016;126:163-7. doi: 10.3109/00207454.2014.996640
Shin E, Rogers JT, Devoto P, Björklund A, Carta M. Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease. Exp Neurol 2014;257:25-38. doi: 10.1016/j.expneurol.2014.04.011
Penttinen AM, Suleymanova I, Albert K, Anttila J, Voutilainen MH, Airavaara M. Characterization of a new low-dose 6-hydroxydopamine model of Parkinson's disease in rat. J Neurosci Res 2016;94:318-28. doi: 10.1002/jnr.23708
Sadakierska-Chudy A, Haduch A, Gołembiowska K, Daniel WA. Effects of low doses of intracerebroventricular 6-OHDA on the levels of monoaminergic neurotransmitters in rat brain structures. Pharmacol Rep 2010;62:1225-30.
Szot P, Franklin A, Sikkema C, Wilkinson CW, Raskind MA. Sequential loss of LC noradrenergic and dopaminergic neurons results in a correlation of dopaminergic neuronal number to striatal dopamine concentration. Front Pharmacol 2012;3:184. doi: 10.3389/fphar.2012.00184
Bonetti F, Brombo G, Zuliani G. The relationship between hyperhomocysteinemia and neurodegeneration. Neurodegener Dis Manag 2016;6:133-45. doi: 10.2217/nmt-2015-0008
Wei LK, Sutherland H, Au A, Camilleri E, Haupt LM, Gan SH, et al. A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke. BioMed Res Int 2015;2015:167976. doi: 10.1155/2015/167976
Haghdoost-Yazdi H, Fraidouni N, Faraji A, Jahanihashemi H, Sarookhani M. High intake of folic acid or complex of B vitamins provides anti-Parkinsonism effect: no role for serum level of homocysteine. Behav Brain Res 2012;233:375-81. doi: 10.1016/j.bbr.2012.05.011
Haghdoost-Yazdi H, Sarookhani M, Faraji A, Fraidouni N, Dargahi T, Yaghoubidoust MH, et al. Evaluation of the association between blood homocysteine concentration and the degree of behavioral symptoms in the 6-hydroxydopamine-induced Parkinsonism in rat. Pharmacol Biochem Behav 2014;124:297-304. doi: 10.1016/j.pbb.2014 .06.020
Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 2001;65:135-72.
Rodriquez M, Barroso-Chinea P, Abdala P, Obeso J, González-Hernández T. Dopamine cell degeneration induced by intraventricular administration of 6-hydroxydopamine in the rat: similarities with cell loss. Exp Neurol 2001;169:163-81. doi: 10.1006/exnr.2000.7624
Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003;39:889-909.
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. San Diego, CA: Academic Press;2007.
Jönsson ME, Ono Y, Björklund A, Thompson LH. Identification of transplantable dopamine neuron precursors at different stages of midbrain neurogenesis. Exp Neurol 2009; 219:341-54. doi: 10.1016/j.expneurol.2009.06.006
Rath A, Klein A, Papazoglou A, Pruszak J, Garcia J, Krause M, Maciaczyk J, et al. Survival and functional restoration of human fetal ventral mesencephalon following transplantation in a rat model of Parkinson's disease.Cell Transplant 2013;22:1281-93. doi: 10.3727/096368912X654984
Martins PJ, Galdieri LC, Souza FG, Andersena ML, Benedito-Silva AA, Tufika S, et al. Physiological variation in plasma total homocysteine concentrations in rats. Life Sci 2005;76:2621-9. doi: 10.1016/j.lfs.2004.12.011
Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 2000;3:1301-6. doi: 10.1038/81834
Lamberti P, Zoccolella S, Iliceto G, Armenise E, Fraddosio A, de Mari M, et al. Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients. Mov Disord 2005;20:69-72. doi: 10.1002/mds.20261
Siniscalchi A, Mancuso F, Gallelli L, Ferreri Ibbadu G, Biagio Mercuri N, De Sarro G. Increase in plasma homocysteine levels induced by drug treatments in neurologic patients. Pharmacol Res 2005;52:367-75. doi: 10.1016/j.phrs.2005.05.013
Segura-Aguilar J, Kostrzewa RM. Neurotoxin mechanisms and processes relevant to Parkinson's disease: an update. Neurotox Res 2015;27:328-54. doi: 10.1007/s12640-015-9519-y
چاپ شده
شماره
نوع مقاله
مجوز
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.