Possible bradykinesia occurrence in lymphocyte division in Parkinson's disease

Year 2024, Volume: 41 Issue: 1, 86 - 91, 29.03.2024

Yağmur İnalkaç Gemici , İrem Taşcı , Muhammed Dündar , Nazmi Özgen , Harika Gözükara Bağ , Ahmet Koç

Abstract

Lymphocytes have dopamine receptors, and low dopamine levels increase receptor synthesis. Lymphocytes may move slower in Parkinson's, which is characterized by low dopamine levels. We hypothesized that longer telomeres would indicate less lymphocyte division. We investigated whether leukocyte telomere length (LTL) is different in naïve Parkinson’s disease (PD) patients and whether telomere length has clinical significance in determining telomere length in naïve Parkinson's patients. Naïve patients diagnosed with PD were included in this study. 29 naïve PD patients and 15 controls were included in the study. Subgroup analyses were performed according to MMSE and depression scores of PD patients. LTL was measured by RT-qPCR. Differences in LTL between the groups were examined. Clinical and demographic findings and LTL were examined and correlated using appropriate statistical methods. Forty-four participants meeting the inclusion criteria were included in the study. LTL was significantly longer in PD patients than in the control group (p = 0.043) and was positively correlated with clinical worsening of the disease. According to the Analysis of Moment Structures, evaluation total MMSE was 1.82, UPDRS was -1.53, and depression score was -.31 negatively correlated with telomere. LTL was found to be longer in naïve PD patients than in controls. Without other factors that could affect telomere; these findings support the hypothesis that leukocyte division could be slower in PD than the control group at the same age. Additional studies are needed on this subject. Additionally, a longer TL could be a marker for a better clinical course in PD.

Keywords

biomarkers, cognitive dysfunction, Parkinson

Ethical Statement

Etik kurul onayı alınmıştır.

Supporting Institution

İnönü Üniversitesi Tıp fakültesi Bilimsel Araştırma PRojeleri Birimi

Project Number

2020/05

Thanks

İnönü Üniversitesi Tıp fakültesi Bilimsel Araştırma PRojeleri Birimi TDK-2020-2263 numarasıyla desteklemiştir.

References

• DeMaagd G, Philip A. Parkinson's Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis. P T. 2015 Aug;40(8):504-32.
• Lopez-Doriga A, Valle L, Alonso MH, Aussó S, Closa A, Sanjuan X, et al. Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response. Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):2992-3000. doi: 10.1016/j.bbadis.2018.06.010.
• Victorelli S, Passos JF. Telomeres and Cell Senescence - Size Matters Not. EBioMedicine. 2017 Jul;21:14-20. doi: 10.1016/j.ebiom.2017.03.027.
• Oeseburg H, de Boer RA, van Gilst WH, van der Harst P. Telomere biology in healthy aging and disease. Pflugers Arch. 2010 Jan;459(2):259-68. doi: 10.1007/s00424-009-0728-1.
• Vaziri H, Schächter F, Uchida I, Wei L, Zhu X, Effros R, et al. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet. 1993 Apr;52(4):661-7.
• Rizvi S, Raza ST, Mahdi F. Telomere length variations in aging and age-related diseases. Curr Aging Sci. 2014;7(3):161-7. doi: 10.2174/1874609808666150122153151.
• Forero DA, González-Giraldo Y, López-Quintero C, Castro-Vega LJ, Barreto GE, Perry G. Telomere length in Parkinson's disease: A meta-analysis. Exp Gerontol. 2016 Mar;75:53-5. doi: 10.1016/j.exger.2016.01.002.
• Yaffe K, Lindquist K, Kluse M, Cawthon R, Harris T, Hsueh WC, et al. Health ABC Study. Telomere length and cognitive function in community-dwelling elders: findings from the Health ABC Study. Neurobiol Aging. 2011 Nov;32(11):2055-60. doi: 10.1016/j.neurobiolaging.2009.12.006.
• Rohn TT. Targeting alpha-synuclein for the treatment of Parkinson's disease. CNS Neurol Disord Drug Targets. 2012 Mar;11(2):174-9. doi: 10.2174/187152712800269678. PMID: 22483285.
• Pajares M, I Rojo A, Manda G, Boscá L, Cuadrado A. Inflammation in Parkinson's Disease: Mechanisms and Therapeutic Implications. Cells. 2020 Jul 14;9(7):1687. doi: 10.3390/cells9071687.
• Keskinoglu P, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State Examination (rMMSE-T) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 2009 Nov;24(11):1242-50. doi: 10.1002/gps.2252.
• Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002 May 15;30(10):e47. doi: 10.1093/nar/30.10.e47.
• Lin J, Smith DL, Esteves K, Drury S. Telomere length measurement by qPCR - Summary of critical factors and recommendations for assay design. Psychoneuroendocrinology. 2019 Jan;99:271-278. doi: 10.1016/j.psyneuen.2018.10.005.
• Schürks M, Buring J, Dushkes R, Gaziano JM, Zee RY, Kurth T. Telomere length and Parkinson's disease in men: a nested case-control study. Eur J Neurol. 2014;21(1):93-9. doi: 10.1111/ene.12252.
• Wu Y, Pei Y, Yang Z, Li K, Lou X, Cui W. Accelerated telomere shortening independent of LRRK2 variants in Chinese patients with Parkinson's disease. Aging (Albany NY). 2020 Oct 29;12(20):20483-20492. doi: 10.18632/aging.103878.
• Chen R, Zhan Y. Association between telomere length and Parkinson's disease: a Mendelian randomization study. Neurobiol Aging. 2021 Jan;97:144.e9-144.e11. doi: 10.1016/j.neurobiolaging.2020.07.019.
• González-Giraldo Y, Garzón-Benitez AV, Forero DA, Barreto GE. TERT inhibition leads to reduction of IL-6 expression induced by palmitic acid and interferes with the protective effects of tibolone in an astrocytic cell model. J Neuroendocrinol. 2019 Aug;31(8):e12768. doi: 10.1111/jne.12768.
• Pacheco R, Contreras F, Zouali M. The dopaminergic system in autoimmune diseases. Front Immunol. 2014 Mar 21;5:117. doi: 10.3389/fimmu.2014.00117.
• Liu Y, Chen Q, Jeong HW, Han D, Fabian J, Drexler HCA, et al. Dopamine signaling regulates hematopoietic stem and progenitor cell function. Blood. 2021 Nov 25;138(21):2051-2065. doi: 10.1182/blood.2020010419.
• Barbanti P, Fabbrini G, Ricci A, Bruno G, Cerbo R, Bronzetti E, et al. Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer's disease. Mech Ageing Dev. 2000 Dec 1;120(1-3):65-75. doi: 10.1016/s0047-6374(00)00183-4.
• Jensen MP, Jacobs BM, Dobson R, Bandres-Ciga S, Blauwendraat C, Schrag A, et al.; International Parkinson's Disease Genomics Consortium (IPDGC). Lower Lymphocyte Count is Associated With Increased Risk of Parkinson's Disease. Ann Neurol. 2021 Apr;89(4):803-812. doi: 10.1002/ana.26034.
• Leibel DK, Shaked D, Beatty Moody DL, Liu HB, Weng NP, Evans MK, et al. Telomere length and cognitive function: Differential patterns across sociodemographic groups. Neuropsychology. 2020 Feb;34(2):186-198. doi: 10.1037/neu0000601.
• Wikgren M, Karlsson T, Söderlund H, Nordin A, Roos G, Nilsson LG, et al. Shorter telomere length is linked to brain atrophy and white matter hyperintensities. Age Ageing. 2014 Mar;43(2):212-7. doi: 10.1093/ageing/aft172.
• Mahoney ER, Dumitrescu L, Seto M, Nudelman KNH, Buckley RF, Gifford KA, et al. Telomere length associations with cognition depend on Alzheimer's disease biomarkers. Alzheimers Dement (N Y). 2019 Dec 9;5:883-890. doi: 10.1016/j.trci.2019.11.003.
• Martin-Ruiz C, Williams-Gray CH, Yarnall AJ, Boucher JJ, Lawson RA, Wijeyekoon RS, et al. Senescence and Inflammatory Markers for Predicting Clinical Progression in Parkinson's Disease: The ICICLE-PD Study. J Parkinsons Dis. 2020;10(1):193-206. doi: 10.3233/JPD-191724.
• Wang L, Koenig HG, Al Shohaib S, Wang Z. Religiosity, depression and telomere length in Chinese older adults. J Affect Disord. 2020 Jan 1;260:624-628. doi: 10.1016/j.jad.2019.09.066.
• Mendes-Silva AP, Vieira ELM, Xavier G, Barroso LSS, Bertola L, Martins EAR, et al. Telomere shortening in late-life depression: A potential marker of depression severity. Brain Behav. 2021 Aug;11(8):e2255. doi: 10.1002/brb3.2255.
• Levstek T, Redenšek S, Trošt M, Dolžan V, Podkrajšek KT. Assessment of the Telomere Length and Its Effect on the Symptomatology of Parkinson's Disease. Antioxidants (Basel). 2021 Jan 19;10(1):137. doi: 10.3390/antiox10010137.