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http://dx.doi.org/10.14406/acu.2021.013

Increased Slc6a4 Expression Associated with Decreased Dopaminergic Neurons in an MPTP Induced Parkinsonism Mouse Model  

Yeo, Sujung (Department of Meridian & Acupoint, College of Korean Medicine, Sangji University)
Publication Information
Korean Journal of Acupuncture / v.38, no.3, 2021 , pp. 133-139 More about this Journal
Abstract
Objectives : Parkinson's disease is a neurodegenerative disease caused by a decrease in the dopaminergic neurons in the substantia nigra. The abnormal expression of solute carrier family 6 member 4 (Slc6a4) has been reported in patients with Parkinson's disease. Methods : In this study, we used MPTP to examine the changes in the expression of Slc6a4 in the brain of mice with Parkinson's disease and investigate its effect on dopaminergic neuronal cell death. Results : In the examination of the Slc6a4 expression in the substantia nigra of MPTP-treated mice for 4 weeks. The gene expression was increased compared to the normal group. To investigate the relationship between Slc6a4 and dopaminergic neurons, we performed a study using siRNA of Slc6a4 in the dopaminergic neuronal cell line SH-SY5Y. Using the siRNA of Slc6a4 to evaluate gene expression, it revealed that the tyrosine hydroxylase (TH) expression increases when Slc6a4 decreases. Moreover, this confirms its effects on the dopaminergic neurons. Additionally, through the evaluation of factors related to apoptosis, in particular, it was established that the value of bax/bcl2 decreased and was affected. These results suggest that a decreased Slc6a4 expression induces an increase in TH expression, providing a mechanism of action for dopaminergic neurons regulated by Slc6a4 expression. Conclusions : Slc6a4 is deemed to be involved in the regulation of dopaminergic neurons, suggesting that an increased Slc6a4 expression induced by MPTP may influence a reduction of dopaminergic neurons.
Keywords
Parkinson's disease; slc6a4; MPTP; MPP+;
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1 Del Rey NL, Quiroga-Varela A, Garbayo E, Carballo-Carbajal I, Fernandez-Santiago R, Monje MHG, et al. Advances in Parkinson's Disease: 200 Years Later. Front Neuroanat. 2018 ; 12 : 113. https://doi.org/10.3389/fnana.2018.00113   DOI
2 Cacciatore I, Ciulla M, Marinelli L, Eusepi P, Di Stefano A. Advances in prodrug design for Parkinson's disease. Expert Opin Drug Discov. 2018 ; 13(4) : 295-305. https://doi.org/10.1080/17460441.2018.1429400   DOI
3 Montanez S, Daws LC, Gould GG, Frazer A. Serotonin (5-HT) transporter (SERT) function after graded destruction of serotonergic neurons. J Neurochem. 2003 ; 87(4) : 861-7. https://doi.org/10.1046/j.1471-4159.2003.02032.x   DOI
4 Martel F, Monteiro R, Lemos C. Uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells occurs through the neuronal serotonin transporter (SERT). J Pharmacol Exp Ther. 2003 ; 306(1) : 355-62. https://doi.org/10.1124/jpet.103.049668   DOI
5 Koren G, Ornoy A. Clinical implications of selective serotonin reuptake inhibitors-selective serotonin norepinephrine reuptake inhibitors pharmacogenetics during pregnancy and lactation. Pharmacogenomics. 2018 ; 19(14) : 1139-45. https://doi.org/10.2217/pgs-2018-0076   DOI
6 Wang JY, Fan QY, He JH, Zhu SG, Huang CP, Zhang X, et al. SLC6A4 Repeat and Single-Nucleotide Polymorphisms Are Associated With Depression and Rest Tremor in Parkinson's Disease: An Exploratory Study. Front Neurol. 2019 ; 10 : 333. https://doi.org/10.3389/fneur.2019.00333   DOI
7 Murphy DL, Fox MA, Timpano KR, Moya PR, Ren-Patterson R, Andrews AM, et al. How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems. Neuropharmacology. 2008 ; 55(6) : 932-60. https://doi.org/10.1016/j.neuropharm.2008.08.034   DOI
8 Zahavi AY, Sabbagh MA, Washburn D, Mazurka R, Bagby RM, Strauss J, et al. Serotonin and Dopamine Gene Variation and Theory of Mind Decoding Accuracy in Major Depression: A Preliminary Investigation. PLoS One. 2016 ; 11(3) : e0150872. https://doi.org/10.1371/journal.pone.0150872   DOI
9 Albani D, Vittori A, Batelli S, Polito L, De Mauro S, Galimberti D, et al. Serotonin transporter gene polymorphic element 5-HTTLPR increases the risk of sporadic Parkinson's disease in Italy. Eur Neurol. 2009 ; 62(2) : 120-3. https://doi.org/10.1159/000222784   DOI
10 Mossner R, Schmitt A, Syagailo Y, Gerlach M, Riederer P, Lesch KP. The serotonin transporter in Alzheimer's and Parkinson's disease. J Neural Transm Suppl. 2000 ; (60) : 345-50.
11 Choi YG, Lim S. N(varepsilon)-(carboxymethyl)lysine linkage to alpha-synuclein and involvement of advanced glycation end products in alpha-synuclein deposits in an MPTP-intoxicated mouse model. Biochimie. 2010 ; 92(10) : 1379-86. https://doi.org/10.1016/j.biochi.2010.06.025   DOI
12 Paus S, Seeger G, Brecht HM, Koster J, El-Faddagh M, Nothen MM, et al. Association study of dopamine D2, D3, D4 receptor and serotonin transporter gene polymorphisms with sleep attacks in Parkinson's disease. Mov Disord. 2004 ; 19(6) : 705-7. https://doi.org/10.1002/mds.20134   DOI
13 Wile DJ, Agarwal PA, Schulzer M, Mak E, Dinelle K, Shahinfard E, et al. Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies. Lancet Neurol. 2017 ; 16(5) : 351-9. https://doi.org/10.1016/s1474-4422(17)30056-x   DOI
14 Elkouzi A, Vedam-Mai V, Eisinger RS, Okun MS. Emerging therapies in Parkinson disease - repurposed drugs and new approaches. Nat Rev Neurol. 2019 ; 15(4) : 204-23. https://doi.org/10.1038/s41582-019-0155-7   DOI
15 Tysnes OB, Storstein A. Epidemiology of Parkinson's disease. J Neural Transm (Vienna). 2017 ; 124(8) : 901-5. https://doi.org/10.1007/s00702-017-1686-y   DOI