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

Simona Damiano,Roberto Paternò,Giovanna Trinchese,Concetta Sozio,Giuliana La Rosa,Mariarosaria Santillo,Maddalena Raia,Maria Pina Mollica,Vittorio Enrico Avvedimento,Gina Cavaliere

doi:10.3390/ijms22052621

Simona Damiano, Roberto Paternò + Show 8 more

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https://doi.org/10.3390/ijms22052621

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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.

Highlights

Oligodendrocyte (OLs) are glial cells of the CNS involved in the formation of myelin sheath around neuron axons
During CNS development, OL originates from Oligodendrocyte Progenitor Cells (OPC) deriving in turn from neural progenitor cells (NPCs) [5]
The results showed, in M03-13 oligodendrocytes stimulated with 5-HT 100 μM, an increase in the basal respiration (Figure 7B) and in the maximal respiration measured after injection of the uncoupler agent FCCP, compared to control and M0313 oligodendrocytes stimulated with 5-HT 200 μM (Figure 7C)

Summary

Introduction

Oligodendrocyte (OLs) are glial cells of the CNS involved in the formation of myelin sheath around neuron axons. OL functions are not restricted to myelination but they provide metabolic support to neurons [1]. OLs produce lactate, which can be shuttled through the lactate transporters MCT1, MCT2 and MCT4 [2] to axons to generate metabolic energy in the form of ATP [3]. During CNS development, OL originates from Oligodendrocyte Progenitor Cells (OPC) deriving in turn from neural progenitor cells (NPCs) [5]. This process is regulated by different molecules such as growth factors, cytokines, hormones, and neurotransmitters [6]

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