5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 3

PMID 33807720

Citations 6

Authors

Simona Damiano

Giuliana La Rosa

Concetta Sozio

Gina Cavaliere

Giovanna Trinchese

Maddalena Raia

Roberto Paterno

Maria Pina Mollica

Vittorio Enrico Avvedimento

Mariarosaria Santillo

Affiliations

Soon will be listed here.

Abstract

Inside the adult CNS, oligodendrocyte progenitor cells (OPC) are able to proliferate, migrate and differentiate into mature oligodendrocytes (OLs) which are responsible for the production of myelin sheet and energy supply for neurons. Moreover, in demyelinating diseases, OPCs are recruited to the lesion areas where they undergo differentiation and myelin synthesis. Serotonin (5-hydroxytryptamine, 5-HT) is involved in OLs' development and myelination, but so far the molecular mechanisms involved or the effects of 5-HT on mitochondria function have not yet been well documented. Our data show that 5-HT inhibits migration and proliferation committing cells toward differentiation in an immortalized human oligodendrocyte precursor cell line, M03-13. Migration blockage is mediated by reactive oxygen species (ROS) generation since antioxidants, such as Vit C and Cu-Zn superoxide dismutase, prevent the inhibitory effects of 5-HT on cell migration. 5-HT inhibits OPC migration and proliferation and increases OL phenotypic markers myelin basic protein (MBP) and Olig-2 via protein kinase C (PKC) activation since the inhibitor of PKC, bis-indolyl-maleimide (BIM), counteracts 5-HT effects. NOX inhibitors as well, reverse the effects of 5-HT, indicating that 5-HT influences the maturation process of OPCs by NOX-dependent ROS production. Finally, 5-HT increases mitochondria function and antioxidant activity. The identification of the molecular mechanisms underlying the effects of 5-HT on maturation and energy metabolism of OPCs could pave the way for the development of new treatments for autoimmune demyelinating diseases such as Multiple Sclerosis where oligodendrocytes are the primary target of immune attack.

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References

Rosko L, Smith V, Yamazaki R, Huang J . Oligodendrocyte Bioenergetics in Health and Disease. Neuroscientist. 2018; 25(4):334-343. PMC: 6745601. DOI: 10.1177/1073858418793077. View

Lee J, van de Ven R, Zaganjor E, Ng M, Barakat A, Demmers J . Inhibition of epithelial cell migration and Src/FAK signaling by SIRT3. Proc Natl Acad Sci U S A. 2018; 115(27):7057-7062. PMC: 6142214. DOI: 10.1073/pnas.1800440115. View

Divakaruni A, Paradyse A, Ferrick D, Murphy A, Jastroch M . Analysis and interpretation of microplate-based oxygen consumption and pH data. Methods Enzymol. 2014; 547:309-54. DOI: 10.1016/B978-0-12-801415-8.00016-3. View

Bonora M, De Marchi E, Patergnani S, Suski J, Celsi F, Bononi A . Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process. Cell Death Differ. 2014; 21(8):1198-208. PMC: 4085526. DOI: 10.1038/cdd.2014.35. View

Takebayashi H, Nabeshima Y, Yoshida S, Chisaka O, Ikenaka K, Nabeshima Y . The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages. Curr Biol. 2002; 12(13):1157-63. DOI: 10.1016/s0960-9822(02)00926-0. View

Guo Y, Suo N, Cui X, Yuan Q, Xie X . Vitamin C promotes oligodendrocytes generation and remyelination. Glia. 2018; 66(7):1302-1316. PMC: 6001564. DOI: 10.1002/glia.23306. View

Shen H, Huang N, Reemmer J, Xiao L . Adenosine Actions on Oligodendroglia and Myelination in Autism Spectrum Disorder. Front Cell Neurosci. 2018; 12:482. PMC: 6292987. DOI: 10.3389/fncel.2018.00482. View

Jiang Q, Kaili D, Freeman J, Lei C, Geng B, Tan T . Diabetes inhibits corneal epithelial cell migration and tight junction formation in mice and human via increasing ROS and impairing Akt signaling. Acta Pharmacol Sin. 2019; 40(9):1205-1211. PMC: 6786421. DOI: 10.1038/s41401-019-0223-y. View

McCord J, Fridovich I . Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969; 244(22):6049-55. View

10.

Damiano S, Petrozziello T, Ucci V, Amente S, Santillo M, Mondola P . Cu-Zn superoxide dismutase activates muscarinic acetylcholine M1 receptor pathway in neuroblastoma cells. Mol Cell Neurosci. 2012; 52:31-7. DOI: 10.1016/j.mcn.2012.11.001. View

11.

McLaurin J, Trudel G, Shaw I, Antel J, Cashman N . A human glial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype. J Neurobiol. 1995; 26(2):283-93. DOI: 10.1002/neu.480260212. View

12.

Bercury K, Macklin W . Dynamics and mechanisms of CNS myelination. Dev Cell. 2015; 32(4):447-58. PMC: 6715306. DOI: 10.1016/j.devcel.2015.01.016. View

13.

Gallo V, Zhou J, McBain C, Wright P, Knutson P, Armstrong R . Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+ channel block. J Neurosci. 1996; 16(8):2659-70. PMC: 6578780. View

14.

Viggiano A, Seru R, Damiano S, De Luca B, Santillo M, Mondola P . Inhibition of long-term potentiation by CuZn superoxide dismutase injection in rat dentate gyrus: involvement of muscarinic M1 receptor. J Cell Physiol. 2011; 227(8):3111-5. DOI: 10.1002/jcp.23062. View

15.

Accetta R, Damiano S, Morano A, Mondola P, Paterno R, Avvedimento E . Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes. Front Cell Neurosci. 2016; 10:146. PMC: 4889614. DOI: 10.3389/fncel.2016.00146. View

16.

Regmi S, Park S, Ku S, Kim J . Serotonin regulates innate immune responses of colon epithelial cells through Nox2-derived reactive oxygen species. Free Radic Biol Med. 2014; 69:377-89. DOI: 10.1016/j.freeradbiomed.2014.02.003. View

17.

Hasan M, Seo J, Rahaman K, Kang M, Jung B, Kwon O . Increased levels of brain serotonin correlated with MMP-9 activity and IL-4 levels resulted in severe experimental autoimmune encephalomyelitis (EAE) in obese mice. Neuroscience. 2016; 319:168-82. DOI: 10.1016/j.neuroscience.2016.01.045. View

18.

Svegliati Baroni S, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M . Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med. 2006; 354(25):2667-76. DOI: 10.1056/NEJMoa052955. View

19.

Potenza N, Mosca N, Mondola P, Damiano S, Russo A, De Felice B . Human miR-26a-5p regulates the glutamate transporter SLC1A1 (EAAT3) expression. Relevance in multiple sclerosis. Biochim Biophys Acta Mol Basis Dis. 2017; 1864(1):317-323. DOI: 10.1016/j.bbadis.2017.09.024. View

20.

Smith J, Ladi E, Mayer-Proschel M, Noble M . Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell. Proc Natl Acad Sci U S A. 2000; 97(18):10032-7. PMC: 27662. DOI: 10.1073/pnas.170209797. View