1. 5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells
- Author
-
Gina Cavaliere, Giuliana La Rosa, Maddalena Raia, Concetta Sozio, Mariarosaria Santillo, Vittorio Enrico Avvedimento, Giovanna Trinchese, Maria Pina Mollica, Simona Damiano, Roberto Paternò, Damiano, Simona, La Rosa, Giuliana, Sozio, Concetta, Cavaliere, Gina, Trinchese, Giovanna, Raia, Maddalena, Paternò, Roberto, Mollica, Maria Pina, Avvedimento, Vittorio Enrico, and Santillo, Mariarosaria
- Subjects
Serotonin ,proliferation ,oligodendrocyte precursor cells ,Mitochondrion ,migration ,Article ,Catalysis ,5-hydroxytryptamine ,Cell Line ,Inorganic Chemistry ,Superoxide dismutase ,lcsh:Chemistry ,Myelin ,Immune system ,Cell Movement ,Oligodendrocyte precursor cell ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Protein kinase C ,Cell Proliferation ,chemistry.chemical_classification ,reactive oxygen species ,Reactive oxygen species ,biology ,Stem Cells ,Organic Chemistry ,Myelin Basic Protein ,Cell migration ,General Medicine ,NOX ,Oligodendrocyte Transcription Factor 2 ,Mitochondria ,Computer Science Applications ,Cell biology ,Myelin basic protein ,Oligodendroglia ,medicine.anatomical_structure ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Differentiation ,biology.protein ,Reactive oxygen specie ,5-hydroxytryptamine, Differentiation, Migration, Mitochondria, Oligodendrocyte precursor cells, Reactive oxygen species, Cell Proliferation, Myelin Basic Protein, Stem Cells - Abstract
Inside the adult CNS, oligodendrocyte progenitor cells (OPCS) 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.
- Published
- 2021