open access

Vol 82, No 4 (2023)
Original article
Submitted: 2022-09-17
Accepted: 2022-11-03
Published online: 2022-11-29
Get Citation

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

G. El-Akabawy123, S. O.F. El Kersh4, L. A. Rashed5, S. N. Amin67, A. A.K. El-Sheikh8
·
Pubmed: 36472399
·
Folia Morphol 2023;82(4):841-853.
Affiliations
  1. Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman, United Arab Emirates
  2. Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
  3. Department of Anatomy and Embryology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
  4. Faculty of Medicine, Galala University, Suez, Egypt
  5. Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt
  6. Department of Anatomy, Physiology, and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
  7. Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
  8. Basic Health Sciences Department, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia

open access

Vol 82, No 4 (2023)
ORIGINAL ARTICLES
Submitted: 2022-09-17
Accepted: 2022-11-03
Published online: 2022-11-29

Abstract

Background: Ageing is the primary risk factor for Parkinson’s disease. Progressive
motor and coordination decline that occurs with ageing has been linked to nigrostriatal
dysfunction. Few studies have investigated the efficacy of mesenchymal
stem cells in ameliorating the structural and functional alterations in the ageing
nigrostriatal system. This study is the first to evaluate the effects of intravenous
injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-
induced rat model of nigrostriatal ageing.
Materials and methods: BMMSCs were intravenously injected once every
2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and
differentiated into dopaminergic neurones and astrocytes.
Results: BMMSC transplantation improved locomotor activity, restored dopaminergic
system function, preserved atrophic dopaminergic neurones in the substantia
nigra, exerted antioxidative effects, and restored neurotrophic factors.
Conclusions: Our findings demonstrate the efficacy of BMMSC injection in
a nigrostriatal ageing rat model, and suggest that these cells may provide an effective
therapeutic approach for the ageing nigrostriatal system.

Abstract

Background: Ageing is the primary risk factor for Parkinson’s disease. Progressive
motor and coordination decline that occurs with ageing has been linked to nigrostriatal
dysfunction. Few studies have investigated the efficacy of mesenchymal
stem cells in ameliorating the structural and functional alterations in the ageing
nigrostriatal system. This study is the first to evaluate the effects of intravenous
injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-
induced rat model of nigrostriatal ageing.
Materials and methods: BMMSCs were intravenously injected once every
2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and
differentiated into dopaminergic neurones and astrocytes.
Results: BMMSC transplantation improved locomotor activity, restored dopaminergic
system function, preserved atrophic dopaminergic neurones in the substantia
nigra, exerted antioxidative effects, and restored neurotrophic factors.
Conclusions: Our findings demonstrate the efficacy of BMMSC injection in
a nigrostriatal ageing rat model, and suggest that these cells may provide an effective
therapeutic approach for the ageing nigrostriatal system.

Get Citation

Keywords

bone marrow-mesenchymal stem cells, D-galactose, rat, nigrostriatal dysfunction

About this article
Title

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

Journal

Folia Morphologica

Issue

Vol 82, No 4 (2023)

Article type

Original article

Pages

841-853

Published online

2022-11-29

Page views

967

Article views/downloads

622

DOI

10.5603/FM.a2022.0097

Pubmed

36472399

Bibliographic record

Folia Morphol 2023;82(4):841-853.

Keywords

bone marrow-mesenchymal stem cells
D-galactose
rat
nigrostriatal dysfunction

Authors

G. El-Akabawy
S. O.F. El Kersh
L. A. Rashed
S. N. Amin
A. A.K. El-Sheikh

References (72)
  1. Ababneh NA, Al-Kurdi B, Jamali F, et al. A comparative study of the capability of MSCs isolated from different human tissue sources to differentiate into neuronal stem cells and dopaminergic-like cells. PeerJ. 2022; 10: e13003.
  2. Abdelwahab SA, Elsebay SA, Ibrahim MF, et al. Cerebral and cerebellar histological changes in the rat animal model of rotenone induced parkinsonism can be ameliorated by bone marrow derived stem cell conditioned media. J Chem Neuroanat. 2021; 111: 101892.
  3. Artegiani B, Calegari F. Age-related cognitive decline: can neural stem cells help us? Aging (Albany NY). 2012; 4(3): 176–186.
  4. Bäckman L, Nyberg L, Lindenberger U, et al. The correlative triad among aging, dopamine, and cognition: current status and future prospects. Neurosci Biobehav Rev. 2006; 30(6): 791–807.
  5. Badyra B, Sułkowski M, Milczarek O, et al. Mesenchymal stem cells as a multimodal treatment for nervous system diseases. Stem Cells Transl Med. 2020; 9(10): 1174–1189.
  6. Baquet ZC, Bickford PC, Jones KR. Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci. 2005; 25(26): 6251–6259.
  7. Barker RA, Björklund A, Gash DM, et al. GDNF and Parkinson's disease: where next? A summary from a recent workshop. J Parkinsons Dis. 2020; 10(3): 875–891.
  8. Behfar Q, Ramirez Zuniga A, Martino-Adami PV. Aging, Senescence, and Dementia. J Prev Alzheimers Dis. 2022; 9(3): 523–531.
  9. Berebichez-Fridman R, Montero-Olvera PR. Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J. 2018; 18(3): e264–e277.
  10. Blinkouskaya Y, Caçoilo A, Gollamudi T, et al. Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev. 2021; 200: 111575.
  11. Boger HA, Mannangatti P, Samuvel DJ, et al. Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging. Genes Brain Behav. 2011; 10(2): 186–198.
  12. Bouchez G, Sensebé L, Vourc'h P, et al. Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease. Neurochem Int. 2008; 52(7): 1332–1342.
  13. Cao N, Liao T, Liu J, et al. Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis. Cell Death Dis. 2017; 8(8): e2996.
  14. Dluzen DE, McDermott JL, Anderson LI, et al. Age-related changes in nigrostriatal dopaminergic function are accentuated in +/- brain-derived neurotrophic factor mice. Neuroscience. 2004; 128(1): 201–208.
  15. El-Akabawy G, Aabed K, Rashed LA, et al. Preventive effects of bone marrow-derived mesenchymal stem cell transplantation in a D-galactose-induced brain aging in rats. Folia Morphol. 2022; 81(3): 632–649.
  16. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82(1): 70–77.
  17. Febbraro F, Andersen KJ, Sanchez-Guajardo V, et al. Chronic intranasal deferoxamine ameliorates motor defects and pathology in the α-synuclein rAAV Parkinson's model. Exp Neurol. 2013; 247: 45–58.
  18. Fernández CI, Alberti E, Mendoza Y, et al. Motor and cognitive recovery induced by bone marrow stem cells grafted to striatum and hippocampus of impaired aged rats: functional and therapeutic considerations. Ann N Y Acad Sci. 2004; 1019: 48–52.
  19. Foltynie T, Sawcer S, Brayne C, et al. The genetic basis of Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002; 73(4): 363–370.
  20. Ghahari L, Safari M, Rahimi Jaberi K, et al. Mesenchymal stem cells with granulocyte colony-stimulating factor reduce stress oxidative factors in Parkinson's disease. Iran Biomed J. 2020; 24(2): 89–98.
  21. Giacobbo BL, Özalay Ö, Mediavilla T, et al. The aged striatum: evidence of molecular and structural changes using a longitudinal multimodal approach in mice. Front Aging Neurosci. 2022; 14: 795132.
  22. Goldstein LB. Rapid reliable measurement of lesion parameters for studies of motor recovery after sensorimotor cortex injury in the rat. J Neurosci Methods. 1993; 48(1-2): 35–42.
  23. Hou Y, Dan X, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol. 2019; 15(10): 565–581.
  24. Inden M, Takata K, Nishimura K, et al. Therapeutic effects of human mesenchymal and hematopoietic stem cells on rotenone-treated parkinsonian mice. J Neurosci Res. 2013; 91(1): 62–72.
  25. Ionescu-Tucker A, Cotman CW. Emerging roles of oxidative stress in brain aging and Alzheimer's disease. Neurobiol Aging. 2021; 107: 86–95.
  26. Jiménez-Acosta MA, Hernández LJ, Cristerna ML, et al. Mesenchymal stem cells: new alternatives for nervous system disorders. Curr Stem Cell Res Ther. 2023; 18(3): 299–321.
  27. Juarez EJ, Castrellon JJ, Green MA, et al. Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition. Psychol Aging. 2019; 34(7): 921–932.
  28. Karalija N, Papenberg G, Wåhlin A, et al. Sex differences in dopamine integrity and brain structure among healthy older adults: Relationships to episodic memory. Neurobiol Aging. 2021; 105: 272–279.
  29. Kim D, Kyung J, Park D, et al. Health span-extending activity of human amniotic membrane- and adipose tissue-derived stem cells in F344 rats. Stem Cells Transl Med. 2015; 4(10): 1144–1154.
  30. Li M, Yang J, Cheng O, et al. Effect of TO901317 on GF to promote the differentiation of human bone marrow mesenchymal stem cells into dopamine neurons on Parkinson's disease. Ther Adv Chronic Dis. 2021; 12: 2040622321998139.
  31. Li Y, Li Z, Gu J, et al. Exosomes isolated during dopaminergic neuron differentiation suppressed neuronal inflammation in a rodent model of Parkinson's disease. Neurosci Lett. 2022; 771: 136414.
  32. Li Z, Zhang Z, Ren Y, et al. Aging and age-related diseases: from mechanisms to therapeutic strategies. Biogerontology. 2021; 22(2): 165–187.
  33. Limke TL, Rao MS. Neural stem cells in aging and disease. J Cell Mol Med. 2002; 6(4): 475–496.
  34. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25(4): 402–408.
  35. Lopez-Leon M, Reggiani PC, Claudia B, et al. Regenerative medicine for the aging brain. Enliven: J Stem Cell Res Regen Med. 2014; 01(01).
  36. Lövdén M, Karalija N, Andersson M, et al. Latent-Profile analysis reveals behavioral and brain correlates of dopamine-cognition associations. Cereb Cortex. 2018; 28(11): 3894–3907.
  37. Mahendru D, Jain A, Bansal S, et al. Neuroprotective effect of bone marrow-derived mesenchymal stem cell secretome in 6-OHDA-induced Parkinson's disease. Regen Med. 2021; 16(10): 915–930.
  38. Manfredsson FP, Polinski NK, Subramanian T, et al. The future of GDNF in Parkinson's disease. Front Aging Neurosci. 2020; 12: 593572.
  39. Mendes-Pinheiro B, Anjo SI, Manadas B, et al. Bone marrow mesenchymal stem cells' secretome exerts neuroprotective effects in a Parkinson's disease rat model. Front Bioeng Biotechnol. 2019; 7: 294.
  40. Mercado NM, Collier TJ, Sortwell CE, et al. BDNF in the Aged Brain: Translational Implications for Parkinson's Disease. Austin Neurol Neurosci. 2017; 2(2).
  41. Mickiewicz AL, Kordower JH. GDNF family ligands: a potential future for Parkinson's disease therapy. CNS Neurol Disord Drug Targets. 2011; 10(6): 703–711.
  42. Mitra S, Turconi G, Darreh-Shori T, et al. Increased endogenous GDNF in mice protects against age-related decline in neuronal cholinergic markers. Front Aging Neurosci. 2021; 13: 714186.
  43. Nakagawa T, Yabe T, Schwartz JP. Gene expression profiles of reactive astrocytes cultured from dopamine-depleted striatum. Neurobiol Dis. 2005; 20(2): 275–282.
  44. Naoi M, Maruyama W. Cell death of dopamine neurons in aging and Parkinson's disease. Mech Ageing Dev. 1999; 111(2-3): 175–188.
  45. Nicaise AM, Willis CM, Crocker SJ, et al. Stem cells of the aging brain. Front Aging Neurosci. 2020; 12: 247.
  46. Palasz E, Wysocka A, Gasiorowska A, et al. BDNF as a promising therapeutic agent in parkinson's disease. Int J Mol Sci. 2020; 21(3).
  47. Park D, Yang G, Bae DK, et al. Human adipose tissue-derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice. J Neurosci Res. 2013; 91(5): 660–670.
  48. Piccardi L, Curcio G, Palermo L, et al. Ageing and neurodegenerative disorders. Behav Neurol. 2015; 2015: 149532.
  49. Polisetti N, Chaitanya VG, Babu PP, et al. Isolation, characterization and differentiation potential of rat bone marrow stromal cells. Neurol India. 2010; 58(2): 201–208.
  50. Popescu BO, Toescu EC, Popescu LM, et al. Blood-brain barrier alterations in ageing and dementia. J Neurol Sci. 2009; 283(1-2): 99–106.
  51. Quinn LP, Perren MJ, Brackenborough KT, et al. A beam-walking apparatus to assess behavioural impairments in MPTP-treated mice: pharmacological validation with R-(-)-deprenyl. J Neurosci Methods. 2007; 164(1): 43–49.
  52. Rahbaran M, Zekiy AO, Bahramali M, et al. Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects. Cell Mol Biol Lett. 2022; 27(1): 56.
  53. Rangan GK, Tesch GH. Quantification of renal pathology by image analysis. Nephrology (Carlton). 2007; 12(6): 553–558.
  54. Reeve A, Simcox E, Turnbull D. Ageing and Parkinson's disease: why is advancing age the biggest risk factor? Ageing Res Rev. 2014; 14(100): 19–30.
  55. Schiess M, Suescun J, Doursout MF, et al. Allogeneic bone marrow-derived mesenchymal stem cell safety in idiopathic Parkinson's disease. Mov Disord. 2021; 36(8): 1825–1834.
  56. Seo JP, Koo DK. Aging of the nigrostriatal tract in the human brain: a diffusion tensor imaging study. Medicina (Kaunas). 2021; 57(9).
  57. Shen J, Tsai YT, Dimarco NM, et al. Transplantation of mesenchymal stem cells from young donors delays aging in mice. Sci Rep. 2011; 1: 67.
  58. Shetty P, Ravindran G, Sarang S, et al. Clinical grade mesenchymal stem cells transdifferentiated under xenofree conditions alleviates motor deficiencies in a rat model of Parkinson's disease. Cell Biol Int. 2009; 33(8): 830–838.
  59. Sikora E, Bielak-Zmijewska A, Dudkowska M, et al. Cellular senescence in brain aging. Front Aging Neurosci. 2021; 13: 646924.
  60. Simpson JE, Wharton SB, Cooper J, et al. Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brain. Neurosci Lett. 2010; 486(3): 246–251.
  61. Strome EM, Cepeda IL, Sossi V, et al. Evaluation of the integrity of the dopamine system in a rodent model of Parkinson's disease: small animal positron emission tomography compared to behavioral assessment and autoradiography. Mol Imaging Biol. 2006; 8(5): 292–299.
  62. Trist BG, Hare DJ, Double KL. Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease. Aging Cell. 2019; 18(6): e13031.
  63. Umegaki H, Roth GS, Ingram DK. Aging of the striatum: mechanisms and interventions. Age (Dordr). 2008; 30(4): 251–261.
  64. Wang X, Zhuang W, Fu W, et al. The lentiviral-mediated Nurr1 genetic engineering mesenchymal stem cells protect dopaminergic neurons in a rat model of Parkinson's disease. Am J Transl Res. 2018; 10(6): 1583–1599.
  65. Wills ED. Evaluation of lipid peroxidation in lipids and biologicalmembranes. In: Snell K, Mullock B (Eds.), Biochemical Toxicology: A PracticalApproach. Oxford, London 1987.
  66. Xiong N, Yang H, Liu L, et al. bFGF promotes the differentiation and effectiveness of human bone marrow mesenchymal stem cells in a rotenone model for Parkinson's disease. Environ Toxicol Pharmacol. 2013; 36(2): 411–422.
  67. Xue J, Liu Y, Darabi MA, et al. An injectable conductive Gelatin-PANI hydrogel system serves as a promising carrier to deliver BMSCs for Parkinson's disease treatment. Mater Sci Eng C Mater Biol Appl. 2019; 100: 584–597.
  68. Zappa Villar MF, Lehmann M, García MG, et al. Mesenchymal stem cell therapy improves spatial memory and hippocampal structure in aging rats. Behav Brain Res. 2019; 374: 111887.
  69. Zarbakhsh S, Safari M, Aldaghi MR, et al. Irisin protects the substantia nigra dopaminergic neurons in the rat model of Parkinson's disease. Iran J Basic Med Sci. 2019; 22(7): 722–728.
  70. Zhang J, Yang Bo, Luo L, et al. Effect of NTN and Lmx1 on the notch signaling pathway during the differentiation of human bone marrow mesenchymal stem cells into dopaminergic neuron-like cells. Parkinsons Dis. 2021; 2021: 6676709.
  71. Zheng W, Honmou O, Miyata K, et al. Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia. Brain Res. 2010; 1310: 8–16.
  72. Zia A, Pourbagher-Shahri AM, Farkhondeh T, et al. Molecular and cellular pathways contributing to brain aging. Behav Brain Funct. 2021; 17(1): 6.

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