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Effects of lipoic acid on primary murine microglial cells.

ABSTRACT: The anti-oxidant lipoic acid (LA) is beneficial in murine models of multiple sclerosis (MS) and has recently been shown to slow brain atrophy in secondary progressive MS. The mechanism of these effects by LA is incompletely understood but may involve effects on microglia. The objective of this study is to understand how LA affects microglial cells. We cultured primary microglial cells from C57BL/6 adult mice brains and stimulated the cells with lipopolysaccharide (LPS) and interferon gamma (IFN-?) in the presence or absence of LA. We demonstrate the inhibition of phagocytosis, rearrangement of actin, and formation of membrane blebs in stimulated microglia in the presence of LA. These experiments suggest that LA causes changes in microglial actin, which may lead to alterations in phagocytosis, mobility, and migration.

SUBMITTER: Chaudhary P

PROVIDER: S-EPMC6660368 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Effects of lipoic acid on primary murine microglial cells.

Chaudhary Priya P Marracci Gail G Pocius Edvinas E Galipeau Danielle D Morris Brooke B Bourdette Dennis D

Journal of neuroimmunology 20190527

The anti-oxidant lipoic acid (LA) is beneficial in murine models of multiple sclerosis (MS) and has recently been shown to slow brain atrophy in secondary progressive MS. The mechanism of these effects by LA is incompletely understood but may involve effects on microglia. The objective of this study is to understand how LA affects microglial cells. We cultured primary microglial cells from C57BL/6 adult mice brains and stimulated the cells with lipopolysaccharide (LPS) and interferon gamma (IFN- ...[more]

PMID: 31176014

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Project description:Cisplatin, a small platinum-containing molecule, is a widely used, highly effective anticancer drug. However, severe side effects have been found in cancer patients treated with cisplatin, including nephrotoxicity, neurotoxicity, and ototoxicity. These cisplatin-induced side effects can have a major impact on patient quality of life, including social development problems in pediatric patients that develop hearing loss. Previous studies have suggested that the major cause of cisplatin-induced ototoxicity is abnormal accumulation of reactive oxygen species (ROS) and oxidative stress. Alpha-lipoic acid (ALA), one of the most effective antioxidants, is known to be involved in the cellular antioxidant system and may have a protective effect on cisplatin-induced ototoxicity. However, the therapeutic effect of ALA on damaged hearing function and its detailed mechanism of action are not fully understood. This study focused on determining whether ALA has a potential as a protective and/or therapeutic agent for cisplatin-induced ototoxicity. Histological and physiological analyses were performed using cisplatin-treated mouse cochlea and HEI-OC1 culture cells in pre- and post-treatment with ALA in vitro and in vivo. We found that ALA contributes to protecting mitochondrial function by preventing ROS accumulation and inhibiting apoptotic cell death. Importantly, post-treatment with ALA consistently showed an almost equal restorative effect to pretreatment, in vitro and in vivo, supporting the possible use of ALA as a therapeutic agent for cisplatin-induced ototoxicity. This study is the first report on a strong therapeutic potential of ALA to rescue ototoxic hearing loss caused by cisplatin, and our data provide key evidence that ALA may act as a reducing agent for glutathione disulfide to increase glutathione levels on behalf of glutathione reductase. This result was consistent in both cultured cells and the mouse model, which improves the clinical value of ALA for therapy of cisplatin-induced ototoxicity.

Dataset Information

Effects of lipoic acid on primary murine microglial cells.

Publications

Effects of lipoic acid on primary murine microglial cells.

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