Abstract
Neuroinflammation, whose distinctive sign is the activation of microglia, is supposed to play a key role in the development and progression of neurodegenerative diseases. The aim of this investigation was to determine levels of neurosteroids produced by resting and injured BV-2 microglial cells. BV-2 cells were exposed to increasing concentrations of rotenone to progressively reduce their viability by increasing reactive oxygen species (ROS) production. BV-2 cell viability was significantly reduced 24, 48 and 72 h after rotenone (50–1000 nM) exposure. Concomitantly, rotenone (50–100 nM) determined a dose-independent augmentation of ROS production. Then, BV-2 cells were exposed to a single, threshold dose of rotenone (75 nM) to evaluate the overtime release of neurosteroids. In particular, pregnenolone, pregnenolone sulfate, progesterone, 5α-dihydroprogesterone (5α-DHP), allopregnanolone, and pregnanolone, were quantified in the culture medium by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. BV-2 cells synthesized all the investigated neurosteroids and, after exposure to rotenone, 5αDHP and pregnanolone production was remarkably increased. In conclusion, we found that BV-2 cells not only synthesize several neurosteroids, but further increase this production following oxidative damage. Pregnanolone and 5α-DHP may play a role in modifying the progression of neuroinflammation in neurodegenerative diseases.
Highlights
Microglia are natural immune cells composing up to 10% of the central nervous system (CNS)population, and up to 20% of glial cells [1,2,3]
We provide the first evidence for the synthesis of different neurosteroids in cultivated microglia
Pregnenolone sulfate, progesterone, 5α-DHP, In the present study,we provide pregnenolone, the first evidence for the synthesis of different neurosteroids in allopregnanolone, and pregnanolone significantly changed over time in the culture medium of BV-2 cultivated microglia
Summary
Microglia are natural immune cells composing up to 10% of the central nervous system (CNS)population, and up to 20% of glial cells [1,2,3]. Microglia are natural immune cells composing up to 10% of the central nervous system (CNS). Microglia have been shown to be implicated in development and maintenance of CNS homeostasis, but they become activated and contribute to neuroinflammation and neurodegeneration in case of injury to the nervous tissue [4,5,6]. In response to injury microglial cells develop a variety of reactive phenotypes to tentatively reestablish brain homeostasis and confine neuronal damage [7,8]. In addition to neuronal damage, microglia reactivity can be induced by exposure to neurotoxic agents in a manner independent of neuronal lesion [1]. Microglia are dynamic cells that, when activated, change morphology, and receptor expression and secretion of chemokines and cytokines.
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