Histopathological and oligodendrocyte progenitor cells-associated gene expression changes in the subventricular zone of a mouse model of multiple sclerosis

Document Type : Original Research

Authors
S. M. Mirab
A. Omidi
Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Abstract
Introduction: Multiple sclerosis (MS) stands out as the predominant demyelinating illness impacting various regions of the central nervous system (CNS). As MS advanced, the subventricular zone (SVZ), one of the main neural stem cell niches that produce neurons and glial cells throughout life, progressively becomes empty. To effectively use endogenous repair potential-based treatment techniques, it would be essential to have an understanding of the neuropathological features of SVZ. The current study aimed to explore the SVZ in terms of histopathological and molecular changes in the cuprizone animal model of MS.

Materials and methods: Adult male C57BL/6 mice were divided into two categories including control and cuprizone groups. Control animals received a regular diet and the cuprizone group received a diet containing 0.2% cuprizone for 12 weeks. At the end of the study, the histopathology of the SVZ and the relative gene expression of oligodendrocyte progenitor cells (OPCs) in this area were evaluated.

Results: Histopathological assessment demonstrated an obvious prominent existence of cell population in the SVZ following 12 weeks of cuprizone intoxication. Furthermore, the relative gene expression data revealed a statistically significant increase in the expression of the Pdgf and Cspg4 genes in the SVZ in the cuprizone group compared to the control group (p˂0.001).

Conclusions: The prominent presence of cells as well as the increase of relative gene expression in the SVZ following the cuprizone diet might be attributed to the production of new progenitor cells for oligodendrocytes, which could potentially refill the SVZ area.

Keywords

Subjects

1. Nait-Oumesmar B, Picard-Riera N, Kerninon C, Decker L, Seilhean D, Höglinger GU, et al. Activation of the subventricular zone in multiple sclerosis: evidence for early glial progenitors. Proceedings of the National Academy of Sciences. 2007;104(11):4694-9.
2. Höftberger R, Lassmann H. Inflammatory demyelinating diseases of the central nervous system. Handbook of clinical neurology. 2018;145:263-83.
3. Zhao J-W, Wang D-X, Ma X-R, Dong Z-J, Wu J-B, Wang F, et al. Impaired metabolism of oligodendrocyte progenitor cells and axons in demyelinated lesion and in the aged CNS. Current Opinion in Pharmacology. 2022;64:102205.
4. Tepavčević V, Lubetzki C. Oligodendrocyte progenitor cell recruitment and remyelination in multiple sclerosis: the more, the merrier? Brain. 2022;145(12):4178-92.
5. Maki T, Liang AC, Miyamoto N, Lo EH, Arai K. Mechanisms of oligodendrocyte regeneration from ventricular-subventricular zone-derived progenitor cells in white matter diseases. Frontiers in cellular neuroscience. 2013;7:275.
6. Geribaldi-Doldán N, Carrascal L, Pérez-García P, Oliva-Montero JM, Pardillo-Díaz R, Domínguez-García S, et al. Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair? International Journal of Molecular Sciences. 2023;24(7):6587.
7. Boshans LL, Sherafat A, Nishiyama A. The effects of developmental and current niches on oligodendrocyte precursor dynamics and fate. Neuroscience letters. 2020;715:134593.
8. Nishiyama A, Shimizu T, Sherafat A, Richardson WD, editors. Life-long oligodendrocyte development and plasticity. Seminars in cell & developmental biology; 2021: Elsevier.
9. Zhou B, Zhu Z, Ransom BR, Tong X. Oligodendrocyte lineage cells and depression. Molecular psychiatry. 2021;26(1):103-17.
10. Butt AM, Rivera AD, Fulton D, Azim K. Targeting the subventricular zone to promote myelin repair in the aging brain. Cells. 2022;11(11):1809.
11. Cunniffe N, Coles A. Promoting remyelination in multiple sclerosis. Journal of neurology. 2021;268(1):30-44.
12. Kipp M, Nyamoya S, Hochstrasser T, Amor S. Multiple sclerosis animal models: a clinical and histopathological perspective. Brain pathology. 2017;27(2):123-37.
13. Zirngibl M, Assinck P, Sizov A, Caprariello AV, Plemel JR. Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination. Molecular Neurodegeneration. 2022;17(1):1-28.
14. Sen MK, Mahns DA, Coorssen JR, Shortland PJ. Behavioural phenotypes in the cuprizone model of central nervous system demyelination. Neuroscience & Biobehavioral Reviews. 2019;107:23-46.
15. Morgan ML, Teo W, Hernandez Y, Brideau C, Cummins K, Kuipers HF, et al. Cuprizone-induced Demyelination in Mouse Brain is not due to Depletion of Copper. ASN neuro. 2022;14:17590914221126367.
16. Oh J, Vidal-Jordana A, Montalban X. Multiple sclerosis: clinical aspects. Current opinion in neurology. 2018;31(6):752-9.
17. Kalakh S, Mouihate A. Demyelination-induced inflammation attracts newly born neurons to the white matter. Molecular neurobiology. 2017;54:5905-18.
18. Kang W, Nguyen KC, Hébert JM. Transient redirection of SVZ stem cells to oligodendrogenesis by FGFR3 activation promotes remyelination. Stem Cell Reports. 2019;12(6):1223-31.
19. Badner A, Cummings BJ. The endogenous progenitor response following traumatic brain injury: A target for cell therapy paradigms. Neural regeneration research. 2022;17(11):2351.
Pathobiology Reserach
Volume 25, Issue 3
April 2022
Pages 1-5