Comparison of Assessing the Success of Cell Transplantation in Experimental Parkinson by Measuring Homocysteine with Behavioral Symptoms

Authors

  • Hashem Haghdoost Yazdi1 1- Dept. of Physiology, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Mohammad Sofiabadi2 2- Dept. of Physiology, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Mohammad Sarookhani3 3- Dept. of Laboratory Sciences, School of Paramedicine, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Zahra Babashaverdi4 4- Dept. of Laboratory Sciences, School of Paramedicine, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Nafise Rastgoo5 5- Dept. of Physiology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Ali Sarbazi5 5- Dept. of Physiology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

DOI:

https://doi.org/10.22100/jkh.v11i4.1535

Keywords:

Homocysteine, Parkinson’s disease, 6-hydroxydopamine, Cell replacement therapy.

Abstract

Introduction: Parkinson is a brain’s degenerative disease. Evidence shows that the levels of homocysteine increases in the Parkinson's disease. In this study, the success of cell transplantation was evaluated by comparison between serum homocysteine levels and behavioral symptoms in experimentally Parkinson's induced by 6-hydroxy dopamine (6- OHDA).

Methods: This experimental study was conducted in 2014 on male Wistar rats. The rats initially were Parkinsonism through stereotaxic 6- OHDA microinjection into right middle frontal areas of right hemisphere. Parkinson's was confirmed by apomorphine-induced rotation test. Then the rats treated with stem cell transplantation and the effect of treatment was assessed again. The total level of homocysteine was measured before, six weeks after 6- HDOA injection and ten weeks after cell transplantation. Data were analyzed using paired t-tests, ANOVA and Tukey test.

Results: The total level of homocysteine didn’t change significantly in rats with higher number of rotations. But ten weeks after cell transplantation, the level of homocysteine  decreased significantly.

Conclusion: Considering the direct correlation between the severity of rotational behavior and the degree of lesion in the substantia nigra (SN), our data indicate that higher tHcy values can predict higher SN dopaminergic neurodegeneration.

Author Biographies

  • Mohammad Sofiabadi2, 2- Dept. of Physiology, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
    مرکز تحقيقات سلولي و ملکولي دانشگاه علوم پزشکی قزوین- استادیار
  • Mohammad Sarookhani3, 3- Dept. of Laboratory Sciences, School of Paramedicine, Qazvin University of Medical Sciences, Qazvin, Iran.
    مرکز تحقيقات سلولي و ملکولي دانشگاه علوم پزشکی قزوین

References

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

Published

2017-02-05

Issue

Section

Original Article(s)

How to Cite

Comparison of Assessing the Success of Cell Transplantation in Experimental Parkinson by Measuring Homocysteine with Behavioral Symptoms. (2017). Knowledge and Health in Basic Medical Sciences, 11(4), page:48-55. https://doi.org/10.22100/jkh.v11i4.1535

Most read articles by the same author(s)

<< < 57 58 59 60 61 62 63 64 65 66 > >>