Volume 12, Issue 1 (Vol.12 No.1 Apr 2023)                   rbmb.net 2023, 12(1): 13-26 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mohamed Ibrahim H A, Mohamed Hussein A, Gabr M, El-Saeed R A, Abd-Alhakem Ammar O, Hassan Mosa A A et al . Effect of Melatonin on Alpha Synuclein and Autophagy in Dopaminergic Neuronal Differentiation of Adipose Mesenchymal Stem Cells. rbmb.net 2023; 12 (1) :13-26
URL: http://rbmb.net/article-1-1050-en.html
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Abstract:   (1183 Views)
Background: The current work investigated the effect of melatonin on differentiation of adipose mesenchymal stem cells (AD-MSCs) into dopamine producing cells and its effect on autophagy process and alpha-Synuclein (α-Syn) secretion

Methods: AD-MSCs were characterized by flow cytometry and divided into 4 groups; i) control group (AD-MSCs without any treatment), ii) M+MSCs group (MSCs treated with 1 µM melatonin for 12 days), iii) DN group (MSCs cultured in neurobasal A medium and essential neuronal growth factors for 12 days) and iv) DN+M group (MSCs cultured in neurobasal A medium and 1µM melatonin for 12 days. By the end of experiments, the dopamine and α-Syn levels using ELISA, the expression of MAP-2, m-TOR and α-Syn genes at the level of mRNA and detection of autophagosomes formation using transmission electron microscope were performed. 

Results: We found that the isolated cells were MSCs due to their positivity expression for CD105 and CD90 and negativity expression for CD34 and CD45. The concentration of dopamine was significantly higher and α-Syn concentration was significantly lower in DN+M group when compared to other groups (P< 0.005). Also, this group showed the highly expression for MAP-2 gene and less expression for m-TOR and α-Syn genes (P< 0.005). Moreover, there was significantly increase in autophagosomes formation in this group than another group (P< 0.005). 

Conclusions: It is concluded that the melatonin promotes the differentiation of rat AD-MSCs into dopaminergic cells via induction of autophagy process and reduction of α-Syn secretion.
Full-Text [PDF 456 kb]   (852 Downloads)    
Type of Article: Original Article | Subject: Cell Biology
Received: 2022/09/20 | Accepted: 2023/02/4 | Published: 2023/08/15

References
1. Askar MH, Hussein AM, Al-Basiony SF, Meseha RK, Metias EF, Salama MM, et al. Effects of exercise and ferulic acid on alpha synuclein and neuroprotective heat shock protein 70 in an experimental model of Parkinsonism disease. CNS & Neurol Disor-Drug Targ. 2019;18(2): 156-69.‏ [DOI:10.2174/1871527317666180816095707] [PMID]
2. Mehraein F, Sarbishegi M, Golipoor Z. Different effects of olive leaf extract on antioxidant enzyme activities in midbrain and dopaminergic neurons of Substantia Nigra in young and old rats. Histol Histopathol. 2016;31(4):425-31.
3. Alizadeh R, Bagher Z, Kamrava SK, Falah M, Hamidabadi HG, Boroujeni ME, et al. Differentiation of human mesenchymal stem cells (MSC) to dopaminergic neurons: A comparison between Wharton's Jelly and olfactory mucosa as sources of MSCs. J Chem Neuroanat. 2019;96:126-33. [DOI:10.1016/j.jchemneu.2019.01.003] [PMID]
4. Alizadeh R, Hassanzadeh G, Joghataei MT, Soleimani M, Moradi F, Mohammadpour S, et al. In vitro differentiation of neural stem cells derived from human olfactory bulb into dopaminergic‐like neurons. Eur J Neurosci. 2017;45(6):773-84. [DOI:10.1111/ejn.13504] [PMID]
5. Hussein AM, Eldosoky M, El-Shafey M, El-Mesery M, Ali AN, Abbas KN, et al. Effects of Metformin on Apoptosis and Alpha Synuclein in Rat Model of Pentylenetetrazole-induced Epilepsy. Can J Physiol Pharmacol. 2019; 97(1):37-46. [DOI:10.1139/cjpp-2018-0266] [PMID]
6. Scrivo A, Bourdenx M, Pampliega O, Cuervo AM. Selective autophagy as a potential therapeutic target for neurodegenerative disorders. Lancet Neuro. 2018;17(9):802-815. [DOI:10.1016/S1474-4422(18)30238-2] [PMID]
7. Chen HX, Liang F, Gu P, Xu PL, Xu HJ, Wang WT, et al. Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy. Cell Death & Dis. 2020; 11(4):288. [DOI:10.1038/s41419-020-2473-5] [PMID] [PMCID]
8. Mostafavi H, Forouzandeh M, Bigdeli MR, Nadri S, Eskandari M. Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model Res Squ. 2021; 1-24. [DOI:10.21203/rs.3.rs-974624/v1]
9. Chung TH, Hsu SC, Wu SH, Hsiao JK, Lin CP, Yao M, et al. Dextran- coated iron oxide nanoparticle-improved therapeutic effects of human mesenchymal stem cells in a mouse model of Parkinson's disease. Nanosc. 2018;10(6): 2998-3007. [DOI:10.1039/C7NR06976F] [PMID]
10. Alajez NM, Al-Ali D, Vishnubalaji R, Manikandan M, Alfayez M, Kassem M, et al. Which Stem Cells to Choose for Regenerative Medicine Application: Bone Marrow and Adipose Tissue Stromal Stem Cells - Similarities and Differences. J of Nat & Sci of Med. 2018;1(2):48-54
11. Moon MY, Kim HJ, Choi BY, Sohn M, Chung TN, Suh SW. Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate. Stem Cells Int. 2018; 2018:5736535 [DOI:10.1155/2018/5736535] [PMID] [PMCID]
12. Chi K, Fu RH, Huang YC, Chen SY, Hsu CJ, Lin SZ, et al. Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease. Cell Transplant. 2018;27(3): 456-470. [DOI:10.1177/0963689718757408] [PMID] [PMCID]
13. Muñoz MF, Argüelles S, Medina R, Cano M, Ayala A. Adipose-derived stem cells decreased microglia activation and protected dopaminergic loss in rat lipopolysaccharide model. J Cell Physiol. 2019;234(8):13762-13772. [DOI:10.1002/jcp.28055] [PMID]
14. Hasani S, Boroujeni ME, Aliaghaei A, Baghai K, Rostami A. Dopaminergic induction of human adipose-derived mesenchymal stem cells is accompanied by transcriptional activation of autophagy. Cell Biol Int. 2018;42(12):1688-1694. [DOI:10.1002/cbin.11056] [PMID]
15. Lerner AB, Case JD, Mori W, Wright MR. Melatonin in peripheral nerve. Nat. 1959; 183: 1821. [DOI:10.1038/1831821a0] [PMID]
16. Govindasamy N, Chung Chok K, Ying Ng P, Yian Koh R, Moi Chye S. Melatonin Induced Schwann Cell Proliferation and Dedifferentiation Through NF-ĸB, FAK-Dependent but Src-Independent Pathways. Rep Biochem Mol Biol. 2022;11(1):63-73. [DOI:10.52547/rbmb.11.1.63] [PMID] [PMCID]
17. Mortezaee K, Khanlarkhani N, Sabbaghziarani F, Nekoonam S, Majidpoor J, Hosseini A, et al. Preconditioning with melatonin improves therapeutic outcomes of bone marrow-derived Mesenchymal stem cells in targeting liver fibrosis induced by CCl4. Cell Tissue Res. 2017;369(2): 303-312. [DOI:10.1007/s00441-017-2604-1] [PMID]
18. Zhao L, Hu C, Zhang P, Jiang H, Chen J. Melatonin preconditioning is an effective strategy for mesenchymal stem cell-based therapy for kidney disease. J Cell Mol Med. 2020;24(1):25-33. [DOI:10.1111/jcmm.14769] [PMID] [PMCID]
19. Mohammadi-Mahdiabadi-Hasani MH, Nabiuni M, Parivar K, Yari S, Sahebi AR, Miyan J. The Effects of Embryonic Cerebrospinal Fluid on The Viability and Neuronal Differentiation of Adipose Tissue-Derived Stem Cells in Wistar Rats. Cell J. 2020;22(2):245-252.
20. Phonchai R, Phermthai T, Kitiyanant N, Suwanjang W, Kotchabhakdi N, Chetsawang B. Potential effects and molecular mechanisms of melatonin on the dopaminergic neuronal differentiation of human amniotic fluid mesenchymal stem cells. Neurochem Int. 2019;124:82-93. [DOI:10.1016/j.neuint.2018.12.012] [PMID]
21. Morris JK. A formaldehyde glutaraldehyde fixative of high osmolality for use in electron microscopy. J of Cell Biol. 1965; 27(2):1A-149A.
22. Chia SJ, Tan EK, Chao YX. Historical Perspective: Models of Parkinson's Disease. Int J Mol Sci. 2020; 21(7):2464 [DOI:10.3390/ijms21072464] [PMID] [PMCID]
23. Tirpáková M, Vašíček J, Svoradová A, Baláži A, Tomka M, Bauer M, et al. Phenotypical Characterization and Neurogenic Differentiation of Rabbit Adipose Tissue-Derived Mesenchymal Stem Cells. Gen. 2021;12(3): 431. [DOI:10.3390/genes12030431] [PMID] [PMCID]
24. Zomer HD, Roballo KC, Lessa TB, Bressan FF, Gonçalves NN, Meirelles FV, et al. Distinct features of rabbit and human adipose-derived mesenchymal stem cells: Implications for biotechnology and translational research. Stem Cells Cloning Adv. Appl. 2018;11:43-54. [DOI:10.2147/SCCAA.S175749] [PMID] [PMCID]
25. Zhan XS, El-Ashram S, Luo DZ, Luo HN, Wang BY, Chen SF, et al. A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues. Int J Mol Sci. 2019;20(6):1485. [DOI:10.3390/ijms20061485] [PMID] [PMCID]
26. Bourebaba L, Michalak I, Baouche M, Kucharczyk K, Marycz K. Cladophora glomerata methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome. Stem Cell Res Ther. 2019;10(1): 392. [DOI:10.1186/s13287-019-1499-z] [PMID] [PMCID]
27. Elashry MI, Gegnaw ST, Klymiuk MC, Wenisch S, Arnhold S. Influence of mechanical fluid shear stress on the osteogenic differentiation protocols for Equine adipose tissue-derived mesenchymal stem cells. Acta Histochem. 2019;121(3):344-353. [DOI:10.1016/j.acthis.2019.02.002] [PMID]
28. Machado AK, Homrich SG, Rodrigues CCR, Azzolin VF, Duarte MMMF, Pillar DM, et al. Human adipose-derived stem cells obtained from lipoaspirates are highly susceptible to hydrogen peroxide mediated cytogenotoxicity. Arch Biosci Health. 2019;1(1):11-28. [DOI:10.18593/abh.17060]
29. Bajek A, Gurtowska N, Olkowska J, Kazmierski L, Maj M, Drewa T. Adipose-Derived Stem Cells as a Tool in Cell-Based Therapies. Arch Immunol Ther Exp (Warsz). 2016;64(6):443-454. [DOI:10.1007/s00005-016-0394-x] [PMID] [PMCID]
30. Mo M, Wang S, Zhou Y, Li H, Wu Y. Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential. Cell Mol Life Sci. 2016;73(17):3311-21. [DOI:10.1007/s00018-016-2229-7] [PMID]
31. Hernández R, Jiménez-Luna C, Perales-Adán J, Perazzoli G, Melguizo C, Prados J. Differentiation of Human Mesenchymal Stem Cells towards Neuronal Lineage: Clinical Trials in Nervous System Disorders. Biomol Ther (Seoul). 2020;28(1):34-44. [DOI:10.4062/biomolther.2019.065] [PMID] [PMCID]
32. Moazen B, Zarrinhaghighi A, Nejatollahi F. Selection and Evaluation of Specific Single Chain Antibodies against CD90, a Marker for Mesenchymal and Cancer Stem Cells. Rep Biochem Mol Biol. 2018;7(1):45-51.
33. Khademizadeh M, Messripour M, Ghasemi N, Momen Beik F, Movahedian Attar A. Differentiation of adult human mesenchymal stem cells into dopaminergic neurons. Res Pharm Sci. 2019;14(3):209-215. [DOI:10.4103/1735-5362.258487] [PMID] [PMCID]
34. Urrutia DN, Caviedes P, Mardones R, Minguell JJ, Vega-Letter AM, Jofre CM. Comparative study of the neural differentiation capacity of mesenchymal stromal cells from different tissue sources: An approach for their use in neural regeneration therapies. PLoS One. 2019;14(3):e0213032. [DOI:10.1371/journal.pone.0213032] [PMID] [PMCID]
35. Thangnipon W, Puangmalai N, Suwanna N, Soi-Ampornkul R, Phonchai R, Kotchabhakdi N, et al. Potential role of N-benzylcinnamide in inducing neuronal differentiation from human amniotic fluid mesenchymal stem cells. Neurosci Lett. 2016;610:6-12. [DOI:10.1016/j.neulet.2015.10.050] [PMID]
36. Liu J, Zhou H, Fan W, Dong W, Fu S, He H, Huang F. Melatonin influences proliferation and differentiation of rat dental papilla cells in vitro and dentine formation in vivo by altering mitochondrial activity. J Pineal Res. 2013 Mar;54(2):170-8. [DOI:10.1111/jpi.12002] [PMID] [PMCID]
37. López-Armas G, Flores-Soto ME, Chaparro-Huerta V, Jave-Suarez LF, Soto-Rodríguez S, Rusanova I, et al. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation. Oxid Med Cell Longev. 2016;2016:2136902. [DOI:10.1155/2016/2136902] [PMID] [PMCID]
38. Shu T, Wu T, Pang M, Liu C, Wang X, Wang J, et al. Effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells. Biochem Biophys Res Commun. 2016;474(3):566-571. [DOI:10.1016/j.bbrc.2016.04.108] [PMID]
39. Yousefi B, Sanooghi D, Faghihi F, Joghataei MT, Latifi N. Evaluation of motor neuron differentiation potential of human umbilical cord blood- derived mesenchymal stem cells, in vitro. J Chem Neuroanat. 2017;81:18-26. [DOI:10.1016/j.jchemneu.2017.01.003] [PMID]
40. Riffelmacher T, Simon AK. Mechanistic roles of autophagy in hematopoietic differentiation. FEBS J. 2017;284(7):1008-1020. [DOI:10.1111/febs.13962] [PMID]
41. Tang AH, Rando TA. Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation. EMBO J. 2014;33(23):2782-97. [DOI:10.15252/embj.201488278] [PMID] [PMCID]
42. Wan Y, Zhuo N, Li Y, Zhao W, Jiang D. Autophagy promotes osteogenic differentiation of human bone marrow mesenchymal stem cell derived from osteoporotic vertebrae. Biochem Biophys Res Commun. 2017;488(1):46-52. [DOI:10.1016/j.bbrc.2017.05.004] [PMID]
43. Sotthibundhu A, Nopparat C, Natphopsuk S, Phuthong S, Noisa P, Govitrapong P. Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation. Neurochem Res. 2022;47(9):2580-2590. [DOI:10.1007/s11064-021-03382-2] [PMID]
44. Liu C, Zhou W, Li Z, Ren J, Li X, Li S, et al. Melatonin Protects Neural Stem Cells Against Tri-Ortho-Cresyl Phosphate-Induced Autophagy. Front Mol Neurosci. 2020; 13:25. [DOI:10.3389/fnmol.2020.00025] [PMID] [PMCID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb