Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Sarah-Michelle Orton
 -- 1661 2023-10-24 04:44:03 |
2 format correct
Catherine Yang
 -11 word(s) 1650 2023-10-24 05:48:56 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Sangha, A.; Quon, M.; Pfeffer, G.; Orton, S. Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis. Encyclopedia. Available online: https://encyclopedia.pub/entry/50703 (accessed on 16 November 2024).
Sangha A, Quon M, Pfeffer G, Orton S. Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis. Encyclopedia. Available at: https://encyclopedia.pub/entry/50703. Accessed November 16, 2024.
Sangha, Amarpreet, Michaela Quon, Gerald Pfeffer, Sarah-Michelle Orton. "Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis" Encyclopedia, https://encyclopedia.pub/entry/50703 (accessed November 16, 2024).
Sangha, A., Quon, M., Pfeffer, G., & Orton, S. (2023, October 24). Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis. In Encyclopedia. https://encyclopedia.pub/entry/50703
Sangha, Amarpreet, et al. "Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis." Encyclopedia. Web. 24 October, 2023.
Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis
Edit
This entry is adapted from the peer-reviewed paper 10.3390/nu15132978

Multiple sclerosis (MS) is a complex neurological condition that involves both inflammatory demyelinating and neurodegenerative components. MS research and treatments have traditionally focused on immunomodulation, with less investigation of neuroprotection, and this holds true for the role of vitamin D in MS. Vitamin D plays an anti-inflammatory role in modulating the immune system in MS. More recently, researchers have begun investigating the potential neuroprotective role of vitamin D in MS, which may be important in remyelination and/or the prevention of demyelination. There is a growing body of research uncovering mechanistic role of vitamin D-mediated neuroprotection, including: enhancing oligodendrocyte lineage differentiation, enhancing neurotrophin expression, attenuating aberrant microglial and reactive astrocyte activation, stabilizing the BBB, and reducing oxidative stress. 1,25(OH)2D3 promotes stem cell proliferation and drives the differentiation of neural stem cells into oligodendrocytes, which carry out remyelination. 

vitamin D multiple sclerosis neuroprotection neurodegeneration

1. Vitamin D Promotes Oligodendrocyte Proliferation and Differentiation

Oligodendrocyte dystrophy and apoptosis are significant pathological features in the demyelinating lesions of MS [1]. Oligodendrocytes are myelin-producing glial cells that support neurons in the CNS. During periods of tissue injury, mature oligodendrocytes have the ability to remyelinate CNS neuronal axons to maintain saltatory conduction, which is a prerequisite for proper brain functioning [2]. Remyelination by oligodendrocytes can be robust and restorative, especially in early MS, but declines during later stages of the disease [2][3]. The ability to regenerate the oligodendrocyte population depends on the availability of neural stem cells (NSCs) and oligodendrocyte progenitor cells (OPCs) [2]. Oligodendrogenesis is the process by which NSCs commit to an oligodendrocyte lineage and differentiate into OPCs, which ultimately differentiate into oligodendrocytes [4]. However, in MS, especially during the progressive stage, the regenerative capacity of NSCs and OPCs to give rise to oligodendrocytes is considerably diminished, contributing to neuronal degeneration and impaired axonal conduction [3][5][6]. 
It has previously been shown that OPCs and oligodendrocytes express VDR [7]. VDR-RXR heterodimerization is present in OPCs and is necessary for OPC differentiation [8][9]. The capacity of 1,25(OH)2D3 to promote OPC differentiation is diminished in the presence of a VDR antagonist in a dose-dependent manner [8]. By blocking VDR, it becomes apparent that 1,25(OH)2D3 is exerting its proposed neuroprotective effect on oligodendrocyte lineage cells via VDR-RXR signalling [8]. In 2015, it was demonstrated that VDR is constitutively expressed in NSCs [10]. Increasing vitamin D in vitro upregulates VDR expression in NSCs in a dose-dependent manner [10].
Increased 1,25(OH)2D3 exposure stimulates an increase in NSC proliferation and, importantly, increases the proportion of NSCs that can differentiate into oligodendrocyte lineage cells [10][11] (Figure 1). In a study utilizing a lysolecithin-induced model in the corpus callosum of male rats, the group that received oral 1,25(OH)2D3 had a higher concentration of OPCs at lesion sites compared to sham and control groups [11]. Furthermore, 1,25(OH)2D3 administration increases the proportion of mature oligodendrocytes in a cuprizone-induced demyelination model as well as in NSC and OPC cultures [8][10][12]. Consistent results were found in a murine experimental autoimmune encephalomyelitis (EAE) model, where 1,25(OH)2D3 administration increased the concentration of NSCs, OPCs, and oligodendrocytes [13]. EAE models are often considered more reflective of MS pathogenesis than demyelination models as they exhibit both immune-mediated inflammation and demyelination [14]. Additionally, 1,25(OH)2D3 administration upregulates the expression of myelin basic protein and proteolipid protein, which are markers of myelin content [8][11][12][13]. The upregulation of these markers may suggest that demyelination is reduced and/or remyelination is increased in response to 1,25(OH)2D3 [8][11][12][13].
Figure 1. Overview of the mechanisms involved in neurodegeneration versus vitamin D-mediated neuroprotection in MS. (A) Pathways of neurodegenerative pathogenesis in MS. In addition to the depicted, the expression of neurotrophins and antioxidant enzymes is reduced in neurons and glia. (B) Neuroprotective pathways elicited by vitamin D in MS. Abbreviations: Arg1, arginase 1; BDNF, brain-derived neurotrophic factor; CNTF, ciliary neurotrophic factor; CL-5, claudin-5; GDNF, glial cell line-derived neurotrophic factor; Hmox1, heme oxygenase 1; ICAM-1, intercellular cell adhesion molecule-1; iNOS, inducible nitric oxide synthase; IL, interleukins; MBP, myelin basic protein; NT-3, neurotrophin-3; PLP, proteolipid protein; ROS, reactive oxygen species; VCAM-1, vascular cell adhesion molecule-1; TGF, transforming growth factor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; ZO-1, zonula occluden-1.

2. Enhancing Neurotrophin Expression in Oligodendrocytes

Reduced neurotrophin secretion is another factor that contributes to inadequate neuroprotection in neurodegenerative disorders such as MS [15][16]. Neurotrophins are a family of proteins that elicit protective and regenerative effects by stimulating the proliferation and differentiation of NSCs, as well as the growth, survival, and proper functioning of neuronal and glial cells [15][17][18]. Neurotrophins are secreted by multiple cell types, some of which include oligodendrocytes, among other cell types [10][18][19][20][21]. Key neurotrophins include NT-3, BDNF, CNTF, GDNF, and NGF [17].
Vitamin D has previously been demonstrated to increase neurotrophin expression [22][23][24]. When mouse NSCs were cultured with 1,25(OH)2D3, the expression of NT-3, BDNF, CNTF, and GDNF was upregulated [10]. Consistent results were observed in rodent models showing the upregulation of NGF and BDNF in CNS tissue following 25(OH)D3 supplementation [24][25][26]. In addition, 1,25(OH)2D3 exposure stimulated oligodendrogenesis and neurogenesis in mouse NSCs [10]. This effect may be mediated by the induction of these neurotrophins, whereby 1,25(OH)2D3 enhances NSC proliferation and differentiation into neurons and oligodendrocytes [10]. These neurotrophins have all been previously associated with enhanced oligodendrogenesis and neurogenesis [27][28][29][30][31][32][33]. Overall, increased neurotrophin secretion in response to vitamin D may tip the balance towards a less neurotoxic environment in which CNS cells can more effectively contribute to repair and regeneration (Figure 1).

3. Reducing Reactive Astrogliosis

Astrocytes comprise a large portion of the glial cell population in the CNS [34]. They elicit essential functions, such as metabolically assisting neuronal growth, signalling immune cell entry into the CNS, and forming a critical component of the BBB [34]. When CNS injury occurs, astrocytes become reactive and divide rapidly, also termed astrogliosis, which has both positive and negative consequences [34][35]. Reactive astrocytes aid in recovery by encompassing the site of demyelination, resulting in the construction of a glial scar, which prevents the injury from expanding [36]. However, after a certain point, the abnormal increase in the number of reactive astrocytes is detrimental, as it contributes to the development of MS lesions [34][37][38]. Reactive astrocytes release a number of pro-inflammatory cytokines and ROS, which can be neurotoxic neurons, OPCs, and oligodendrocytes [39].
Reducing the activation and abundance of astrocytes may make the neurodegenerative microenvironment more conducive to repair processes, including the impact on oligodendrocytes [20][40]. MS plaques with fewer reactive astrocytes exhibit elevated OPC content and greater remyelination [40]. The expression of VDR and CYP27B1 were upregulated in the astrocytes of LPS-stimulated rats, supporting a potential response via vitamin D [41]. In rodent models of cuprizone-induced demyelination and LPS injection, it was shown that the concentration and activation of astrocytes were decreased in mice that were administered intraperitoneal injections of 25(OH)D3 and 1,25(OH)2D3 [12][41]. Findings from other rodent CNS disease models have similarly supported a decrease in GFAP expression and astrocyte activation upon supplementation with oral or injected vitamin D [24][41]. More specifically, 25(OH)D3 and 1,25(OH)2D3 downregulated iNOS, TLR4, TNF-α, and IL-1β in cultured astrocytes and EAE [41][42][43] (Figure 1). Additionally, the in vitro exposure of mouse NSCs to 1,25(OH)2D3 reduces NSC differentiation into astrocytes [10] (Figure 1). This is interesting, as vitamin D has the opposite effect of increasing NSC differentiation into oligodendrocytes and neurons (discussed above) [10], consistent with its role in neuroprotection.

4. Stabilizing the Blood–Brain Barrier: impact on oligodendrocytes

The BBB regulates the movement of blood-borne molecules, ions, and cells into the CNS, leading to the stabilization and protection of the neuronal microenvironment [44][45][46][47]. Breakdown of the BBB and consequent hyperpermeability occurs early in MS [48]. When stimulated by pro-inflammatory cytokines from various immune cells, endothelial cells of the BBB downregulate tight junctions and upregulate cell-adhesion molecules, which destabilizes the BBB and increases leukocyte recruitment into the CNS, respectively [49]. Reactive astrocytes also play a role in BBB instability [45][50][51]. Pro-inflammatory cytokines, including TNF-α and IL-1β, secreted from reactive astrocytes stimulate the endothelial cells to downregulate tight junctions and upregulate cell-adhesion molecules [45][50][51]. The reactive astrocytes also detach their endfeet processes from the capillary endothelium, making the BBB more permeable [52]. Interestingly, in a neurodegenerative environment, reactive astrocytes release vascular endothelial growth factor (VEGF), which signals endothelial cells to lower tight junction expression, which destabilizes the BBB [53]. As a result of BBB hyperpermeability, CD4+ Th1 and Th17 cells are able to translocate into the CNS, where their secreted cytokines prompt the degeneration of oligodendrocytes and myelinated axons [48].
Vitamin D is thought to counteract BBB hyperpermeability through multiple mechanisms (Figure 1). In a study using human brain endothelial cells, the effects of 1,25(OH)2D3 exposure were examined following exposure to TNF-α and exposure to sera derived from MS patients [54]. It was found that 1,25(OH)2D3 can act directly on endothelial cells to upregulate tight junction proteins (zonula occluden-1 and claudin-5) and downregulate cell adhesion molecules (ICAM-1 and VCAM-1) [54]. These two outcomes both contribute to BBB stabilization [54]. 
In addition to reducing BBB permeability by upregulating tight junction proteins and downregulating cell-adhesion molecules, 1,25(OH)2D3 has been shown to lower the expression of matrix metalloproteinase-9 (MMP-9) in mouse-brain endothelial cells and in a rat model of ischemic stroke [55][56]. Various cell types, including endothelial cells, CNS cells, and leukocytes, release MMPs [57]. MMPs are responsible for breaking down extracellular matrix components (such as collagen, fibronectin, and laminin) and tight junction proteins, thereby contributing to BBB instability [57][58][59][60]. As such, reducing MMP-9 expression may be another underlying mechanism by which vitamin D promotes BBB stabilization [61]. It has also been demonstrated that 1,25(OH)2D3 reduces the apoptosis of human endothelial cells exposed to MS sera, which may indicate a further protective effect of vitamin D on the BBB [61][62].
In relation to oligodendrocyte-related neuroprotection, Stabilization of the blood brain barrier subsequently helps prevent the degeneration of oligodendrocytes.
Overall, the neuroprotective effects elicited by vitamin D promote a more stable microenvironment in which CNS glial cells can more easily participate in repair and recovery processes. In particular, 1,25(OH)2D3 promotes stem cell proliferation and drives the differentiation of neural stem cells into oligodendrocytes, which carry out remyelination. This could potentially support and restore functioning of neurons in MS.

References

  1. Cudrici, C.; Niculescu, T.; Niculescu, F.; Shin, M.L.; Rus, H. Oligodendrocyte Cell Death in Pathogenesis of Multiple Sclerosis: Protection of Oligodendrocytes from Apoptosis by Complement. J. Rehabil. Res. Dev. 2006, 43, 123–132.
  2. Chamberlain, K.A.; Nanescu, S.E.; Psachoulia, K.; Huang, J.K. Oligodendrocyte Regeneration: Its Significance in Myelin Replacement and Neuroprotection in Multiple Sclerosis. Neuropharmacology 2016, 110, 633–643.
  3. Voskuhl, R.R.; Itoh, N.; Tassoni, A.; Matsukawa, M.A.; Ren, E.; Tse, V.; Jang, E.; Suen, T.T.; Itoh, Y. Gene Expression in Oligodendrocytes during Remyelination Reveals Cholesterol Homeostasis as a Therapeutic Target in Multiple Sclerosis. Proc. Natl. Acad. Sci. USA 2019, 116, 10130–10139.
  4. Armada-Moreira, A.; Ribeiro, F.F.; Sebastião, A.M.; Xapelli, S. Neuroinflammatory Modulators of Oligodendrogenesis. Neuroimmunol. Neuroinflamm. 2015, 2, 263–273.
  5. Rasmussen, S.; Imitola, J.; Ayuso-Sacido, A.; Wang, Y.; Starossom, S.C.; Kivisäkk, P.; Zhu, B.; Meyer, M.; Bronson, R.T.; Garcia-Verdugo, J.M.; et al. Reversible Neural Stem Cell Niche Dysfunction in a Model of Multiple Sclerosis. Ann. Neurol. 2011, 69, 878–891.
  6. Brousse, B.; Magalon, K.; Durbec, P.; Cayre, M. Region and Dynamic Specificities of Adult Neural Stem Cells and Oligodendrocyte Precursors in Myelin Regeneration in the Mouse Brain. Biol. Open 2015, 4, 980–992.
  7. Eyles, D.W.; Smith, S.; Kinobe, R.; Hewison, M.; McGrath, J.J. Distribution of the Vitamin D Receptor and 1 Alpha-Hydroxylase in Human Brain. J. Chem. Neuroanat. 2005, 29, 21–30.
  8. de la Fuente, A.G.; Errea, O.; van Wijngaarden, P.; Gonzalez, G.A.; Kerninon, C.; Jarjour, A.A.; Lewis, H.J.; Jones, C.A.; Nait-Oumesmar, B.; Zhao, C.; et al. Vitamin D Receptor-Retinoid X Receptor Heterodimer Signaling Regulates Oligodendrocyte Progenitor Cell Differentiation. J. Cell Biol. 2015, 211, 975–985.
  9. Huang, J.K.; Jarjour, A.A.; Oumesmar, B.N.; Kerninon, C.; Williams, A.; Krezel, W.; Kagechika, H.; Bauer, J.; Zhao, C.; Evercooren, A.B.V.; et al. Retinoid X Receptor Gamma Signaling Accelerates CNS Remyelination. Nat. Neurosci. 2011, 14, 45–55.
  10. Shirazi, H.A.; Rasouli, J.; Ciric, B.; Rostami, A.; Zhang, G.-X. 1,25-Dihydroxyvitamin D3 Enhances Neural Stem Cell Proliferation and Oligodendrocyte Differentiation. Exp. Mol. Pathol. 2015, 98, 240–245.
  11. Gomez-Pinedo, U.; Cuevas, J.A.; Benito-Martín, M.S.; Moreno-Jiménez, L.; Esteban-Garcia, N.; Torre-Fuentes, L.; Matías-Guiu, J.A.; Pytel, V.; Montero, P.; Matías-Guiu, J. Vitamin D Increases Remyelination by Promoting Oligodendrocyte Lineage Differentiation. Brain Behav. 2019, 10, e01498.
  12. Nystad, A.E.; Wergeland, S.; Aksnes, L.; Myhr, K.-M.; Bø, L.; Torkildsen, Ø. Effect of High-Dose 1.25 Dihydroxyvitamin D3 on Remyelination in the Cuprizone Model. Apmis 2014, 122, 1178–1186.
  13. Shirazi, H.A.; Rasouli, J.; Ciric, B.; Wei, D.; Rostami, A.; Zhang, G.-X. 1,25-Dihydroxyvitamin D3 Suppressed Experimental Autoimmune Encephalomyelitis through Both Immunomodulation and Oligodendrocyte Maturation. Exp. Mol. Pathol. 2017, 102, 515–521.
  14. Denic, A.; Johnson, A.J.; Bieber, A.J.; Warrington, A.E.; Rodriguez, M.; Pirko, I. The Relevance of Animal Models in Multiple Sclerosis Research. Pathophysiology 2011, 18, 21–29.
  15. Kalinowska-Lyszczarz, A.; Losy, J. The Role of Neurotrophins in Multiple Sclerosis-Pathological and Clinical Implications. Int. J. Mol. Sci. 2012, 13, 13713–13725.
  16. Razavi, S.; Nazem, G.; Mardani, M.; Esfandiari, E.; Salehi, H.; Esfahani, S.H.Z. Neurotrophic Factors and Their Effects in the Treatment of Multiple Sclerosis. Adv. Biomed. Res. 2015, 4, 53.
  17. Huang, E.J.; Reichardt, L.F. Neurotrophins: Roles in Neuronal Development and Function. Annu. Rev. Neurosci. 2001, 24, 677–736.
  18. Lu, P.; Jones, L.L.; Snyder, E.Y.; Tuszynski, M.H. Neural Stem Cells Constitutively Secrete Neurotrophic Factors and Promote Extensive Host Axonal Growth after Spinal Cord Injury. Exp. Neurol. 2003, 181, 115–129.
  19. Grajchen, E.; Hendriks, J.J.A.; Bogie, J.F.J. The Physiology of Foamy Phagocytes in Multiple Sclerosis. Acta Neuropathol. Commun. 2018, 6, 124.
  20. Traiffort, E.; Kassoussi, A.; Zahaf, A.; Laouarem, Y. Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions. Front. Cell. Neurosci. 2020, 14, 79.
  21. Xiao, J.; Kilpatrick, T.J.; Murray, S.S. The Role of Neurotrophins in the Regulation of Myelin Development. Neurosignals 2009, 17, 265–276.
  22. Brown, J.; Bianco, J.I.; McGrath, J.J.; Eyles, D.W. 1,25-Dihydroxyvitamin D3 Induces Nerve Growth Factor, Promotes Neurite Outgrowth and Inhibits Mitosis in Embryonic Rat Hippocampal Neurons. Neurosci. Lett. 2003, 343, 139–143.
  23. Naveilhan, P.; Neveu, I.; Wion, D.; Brachet, P. 1,25-Dihydroxyvitamin D3, an Inducer of Glial Cell Line-Derived Neurotrophic Factor. Neuroreport 1996, 7, 2171–2175.
  24. Zou, Y.; Mu, M.; Zhang, S.; Li, C.; Tian, K.; Li, Z.; Li, B.; Wang, W.; Cao, H.; Sun, Q.; et al. Vitamin D3 Suppresses Astrocyte Activation and Ameliorates Coal Dust-Induced Mood Disorders in Mice. J. Affect. Disord. 2022, 303, 138–147.
  25. Khairy, E.Y.; Attia, M.M. Protective Effects of Vitamin D on Neurophysiologic Alterations in Brain Aging: Role of Brain-Derived Neurotrophic Factor (BDNF). Nutr. Neurosci. 2021, 24, 650–659.
  26. Gezen-Ak, D.; Dursun, E.; Yilmazer, S. The Effect of Vitamin D Treatment on Nerve Growth Factor (NGF) Release from Hippocampal Neurons. Noro Psikiyatr. Ars. 2014, 51, 157–162.
  27. Zhu, G.; Sun, C.; Liu, W. Effects of Neurotrophin-3 on the Differentiation of Neural Stem Cells into Neurons and Oligodendrocytes. Neural Regen. Res. 2012, 7, 1483–1487.
  28. Barres, B.A.; Burne, J.F.; Holtmann, B.; Thoenen, H.; Sendtner, M.; Raff, M.C. Ciliary Neurotrophic Factor Enhances the Rate of Oligodendrocyte Generation. Mol. Cell. Neurosci. 1996, 8, 146–156.
  29. Pansri, P.; Phanthong, P.; Suthprasertporn, N.; Kitiyanant, Y.; Tubsuwan, A.; Dinnyes, A.; Kobolak, J.; Kitiyanant, N. Brain-Derived Neurotrophic Factor Increases Cell Number of Neural Progenitor Cells Derived from Human Induced Pluripotent Stem Cells. PeerJ 2021, 9, e11388.
  30. Kokoeva, M.V.; Yin, H.; Flier, J.S. Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy Balance. Science 2005, 310, 679–683.
  31. Gao, X.; Deng, L.; Wang, Y.; Yin, L.; Yang, C.; Du, J.; Yuan, Q. GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat. Stem Cells Int. 2016, 2016, 1431349.
  32. Linker, R.A.; Mäurer, M.; Gaupp, S.; Martini, R.; Holtmann, B.; Giess, R.; Rieckmann, P.; Lassmann, H.; Toyka, K.V.; Sendtner, M.; et al. CNTF Is a Major Protective Factor in Demyelinating CNS Disease: A Neurotrophic Cytokine as Modulator in Neuroinflammation. Nat. Med. 2002, 8, 620–624.
  33. Langhnoja, J.; Buch, L.; Pillai, P. Potential Role of NGF, BDNF, and Their Receptors in Oligodendrocytes Differentiation from Neural Stem Cell: An in Vitro Study. Cell Biol. Int. 2021, 45, 432–446.
  34. Colombo, E.; Farina, C. Astrocytes: Key Regulators of Neuroinflammation. Trends Immunol. 2016, 37, 608–620.
  35. Chiareli, R.A.; Carvalho, G.A.; Marques, B.L.; Mota, L.S.; Oliveira-Lima, O.C.; Gomes, R.M.; Birbrair, A.; Gomez, R.S.; Simão, F.; Klempin, F.; et al. The Role of Astrocytes in the Neurorepair Process. Front. Cell Dev. Biol. 2021, 9, 665795.
  36. Correale, J.; Farez, M.F. The Role of Astrocytes in Multiple Sclerosis Progression. Front. Neurol. 2015, 6, 180.
  37. Holley, J.E.; Gveric, D.; Newcombe, J.; Cuzner, M.L.; Gutowski, N.J. Astrocyte Characterization in the Multiple Sclerosis Glial Scar. Neuropathol. Appl. Neurobiol. 2003, 29, 434–444.
  38. Cristofanilli, M.; Rosenthal, H.; Cymring, B.; Gratch, D.; Pagano, B.; Xie, B.; Sadiq, S.A. Progressive Multiple Sclerosis Cerebrospinal Fluid Induces Inflammatory Demyelination, Axonal Loss, and Astrogliosis in Mice. Exp. Neurol. 2014, 261, 620–632.
  39. Ding, Z.-B.; Song, L.-J.; Wang, Q.; Kumar, G.; Yan, Y.-Q.; Ma, C.-G. Astrocytes: A Double-Edged Sword in Neurodegenerative Diseases. Neural Regen. Res. 2021, 16, 1702–1710.
  40. Chang, A.; Staugaitis, S.M.; Dutta, R.; Batt, C.E.; Easley, K.E.; Chomyk, A.M.; Yong, V.W.; Fox, R.J.; Kidd, G.J.; Trapp, B.D. Cortical Remyelination: A New Target for Repair Therapies in Multiple Sclerosis. Ann. Neurol. 2012, 72, 918–926.
  41. Jiao, K.-P.; Li, S.-M.; Lv, W.-Y.; Jv, M.-L.; He, H.-Y. Vitamin D3 Repressed Astrocyte Activation Following Lipopolysaccharide Stimulation in Vitro and in Neonatal Rats. Neuroreport 2017, 28, 492–497.
  42. Molinari, C.; Morsanuto, V.; Ghirlanda, S.; Ruga, S.; Notte, F.; Gaetano, L.; Uberti, F. Role of Combined Lipoic Acid and Vitamin D3 on Astrocytes as a Way to Prevent Brain Ageing by Induced Oxidative Stress and Iron Accumulation. Oxid. Med. Cell. Longev. 2019, 2019, 2843121.
  43. Garcion, E.; Nataf, S.; Berod, A.; Darcy, F.; Brachet, P. 1,25-Dihydroxyvitamin D3 Inhibits the Expression of Inducible Nitric Oxide Synthase in Rat Central Nervous System during Experimental Allergic Encephalomyelitis. Mol. Brain Res. 1997, 45, 255–267.
  44. Jiang, S.; Xia, R.; Jiang, Y.; Wang, L.; Gao, F. Vascular Endothelial Growth Factors Enhance the Permeability of the Mouse Blood-Brain Barrier. PLoS ONE 2014, 9, e86407.
  45. Elahy, M.; Jackaman, C.; Mamo, J.C.; Lam, V.; Dhaliwal, S.S.; Giles, C.; Nelson, D.; Takechi, R. Blood-Brain Barrier Dysfunction Developed during Normal Aging Is Associated with Inflammation and Loss of Tight Junctions but Not with Leukocyte Recruitment. Immun. Ageing 2015, 12, 2.
  46. Minagar, A.; Alexander, J.S. Blood-Brain Barrier Disruption in Multiple Sclerosis. Mult. Scler. J. 2003, 9, 540–549.
  47. Luissint, A.-C.; Artus, C.; Glacial, F.; Ganeshamoorthy, K.; Couraud, P.-O. Tight Junctions at the Blood Brain Barrier: Physiological Architecture and Disease-Associated Dysregulation. Fluids Barriers CNS 2012, 9, 23.
  48. Lutz, S.E.; Smith, J.R.; Kim, D.H.; Olson, C.V.L.; Ellefsen, K.; Bates, J.M.; Gandhi, S.P.; Agalliu, D. Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation. Cell Rep. 2017, 21, 2104–2117.
  49. Larochelle, C.; Alvarez, J.I.; Prat, A. How Do Immune Cells Overcome the Blood-Brain Barrier in Multiple Sclerosis? FEBS Lett. 2011, 585, 3770–3780.
  50. Cohen, S.S.; Min, M.; Cummings, E.E.; Chen, X.; Sadowska, G.B.; Sharma, S.; Stonestreet, B.S. Effects of Interleukin-6 on the Expression of Tight Junction Proteins in Isolated Cerebral Microvessels from Yearling and Adult Sheep. Neuroimmunomodulation 2013, 20, 264–273.
  51. Kebir, H.; Kreymborg, K.; Ifergan, I.; Dodelet-Devillers, A.; Cayrol, R.; Bernard, M.; Giuliani, F.; Arbour, N.; Becher, B.; Prat, A. Human TH17 Lymphocytes Promote Blood-Brain Barrier Disruption and Central Nervous System Inflammation. Nat. Med. 2007, 13, 1173–1175.
  52. Aharoni, R.; Eilam, R.; Arnon, R. Astrocytes in Multiple Sclerosis-Essential Constituents with Diverse Multifaceted Functions. Int. J. Mol. Sci. 2021, 22, 5904.
  53. Argaw, A.T.; Asp, L.; Zhang, J.; Navrazhina, K.; Pham, T.; Mariani, J.N.; Mahase, S.; Dutta, D.J.; Seto, J.; Kramer, E.G.; et al. Astrocyte-Derived VEGF-A Drives Blood-Brain Barrier Disruption in CNS Inflammatory Disease. J. Clin. Investig. 2012, 122, 2454–2468.
  54. Takahashi, S.; Maeda, T.; Sano, Y.; Nishihara, H.; Takeshita, Y.; Shimizu, F.; Kanda, T. Active Form of Vitamin D Directly Protects the Blood–Brain Barrier in Multiple Sclerosis. Clin. Exp. Neuroimmunol. 2017, 8, 244–254.
  55. Sayeed, I.; Turan, N.; Stein, D.G.; Wali, B. Vitamin D Deficiency Increases Blood-Brain Barrier Dysfunction after Ischemic Stroke in Male Rats. Exp. Neurol. 2019, 312, 63–71.
  56. Won, S.; Sayeed, I.; Peterson, B.L.; Wali, B.; Kahn, J.S.; Stein, D.G. Vitamin D Prevents Hypoxia/Reoxygenation-Induced Blood-Brain Barrier Disruption via Vitamin D Receptor-Mediated NF-KB Signaling Pathways. PLoS ONE 2015, 10, e0122821.
  57. Rosenberg, G.A. Matrix Metalloproteinases Biomarkers in Multiple Sclerosis. Lancet 2005, 365, 1291–1293.
  58. Yabluchanskiy, A.; Ma, Y.; Iyer, R.P.; Hall, M.E.; Lindsey, M.L. Matrix Metalloproteinase-9: Many Shades of Function in Cardiovascular Disease. Physiology 2013, 28, 391.
  59. Yang, Y.; Estrada, E.Y.; Thompson, J.F.; Liu, W.; Rosenberg, G.A. Matrix Metalloproteinase-Mediated Disruption of Tight Junction Proteins in Cerebral Vessels Is Reversed by Synthetic Matrix Metalloproteinase Inhibitor in Focal Ischemia in Rat. J. Cereb. Blood Flow Metab. 2007, 27, 697–709.
  60. Baeten, K.M.; Akassoglou, K. Extracellular Matrix and Matrix Receptors in Blood-Brain Barrier Formation and Stroke. Dev. Neurobiol. 2011, 71, 1018.
  61. Galoppin, M.; Kari, S.; Soldati, S.; Pal, A.; Rival, M.; Engelhardt, B.; Astier, A.; Thouvenot, E. Full Spectrum of Vitamin D Immunomodulation in Multiple Sclerosis: Mechanisms and Therapeutic Implications. Brain Commun. 2022, 4, fcac171.
  62. Dehghani, L.; Meamar, R.; Etemadifar, M.; Sheshde, Z.D.; Shaygannejad, V.; Sharifkhah, M.; Tahani, S. Can Vitamin D Suppress Endothelial Cells Apoptosis in Multiple Sclerosis Patients? Int. J. Prev. Med. 2013, 4, S211.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Clinical Neurology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Amarpreet Sangha
,
Michaela Quon
,
Gerald Pfeffer
,
Sarah-Michelle Orton
View Times: 464
Entry Collection: Neurodegeneration
Revisions: 2 times (View History)
Update Date: 24 Oct 2023
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback