Microglial Cell Morphology and Phagocytic Activity Are Critically Regulated by the Neurosteroid Allopregnanolone: A Possible Role in Neuroprotection.

Valérie Jolivel,Jérôme De Sèze,Fabien Binamé,Christine Patte-Mensah,Susana Brun,Ayikoe-Guy Mensah-Nyagan,Omar Taleb,Dominique Bagnard,Jérémie Benyounes

doi:10.3390/cells10030698

Abstract

Microglial cells are key players in neural pathogenesis and microglial function regulation appears to be pivotal in controlling neuroinflammatory/neurological diseases. Here, we investigated the effects and mechanism of action of neurosteroid allopregnanolone (ALLO) on murine microglial BV-2 cells and primary microglia in order to determine ALLO-induced immunomodulatory potential and to provide new insights for the development of both natural and safe neuroprotective strategies targeting microglia. Indeed, ALLO-treatment is increasingly suggested as beneficial in various models of neurological disorders but the underlying mechanisms have not been elucidated. Therefore, the microglial cells were cultured with various serum concentrations to mimic the blood-brain-barrier rupture and to induce their activation. Proliferation, viability, RT-qPCR, phagocytosis, and morphology analyzes, as well as migration with time-lapse imaging and quantitative morphodynamic methods, were combined to investigate ALLO actions on microglia. BV-2 cells express subunits of GABA-A receptor that mediates ALLO activity. ALLO (10µM) induced microglial cell process extension and decreased migratory capacity. Interestingly, ALLO modulated the phagocytic activity of BV-2 cells and primary microglia. Our results, which show a direct effect of ALLO on microglial morphology and phagocytic function, suggest that the natural neurosteroid-based approach may contribute to developing effective strategies against neurological disorders that are evoked by microglia-related abnormalities.

Highlights

IntroductionMicroglia represent the resident macrophages of the central nervous system (CNS) [1]
Introduction published maps and institutional affilMicroglia represent the resident macrophages of the central nervous system (CNS) [1].They are derived from erythromyeloid progenitors that are found in the yolk bag and they are maintained throughout life without the contribution of adult hematopoiesis [2]
We report the effect of decreasing concentrations of fetal calf serum (FCS) on cell survival, proliferation, morphology, and level of activation of the

Summary

Introduction

Microglia represent the resident macrophages of the central nervous system (CNS) [1]. They are derived from erythromyeloid progenitors that are found in the yolk bag and they are maintained throughout life without the contribution of adult hematopoiesis [2]. Microglia are distributed throughout the whole CNS, where they perform tasks that are essential to development and homeostasis. Their thin and ramified processes are continuously scanning the environment [3,4]. MS represents the most common non-traumatic neurological disorder in young patients.

Methods

Results

Discussion

Conclusion