Neuroprotection of dihydrotestosterone via suppression of the toll-like receptor 4/nuclear factor-kappa B signaling pathway in high glucose-induced BV-2 microglia inflammatory responses

In this study, we investigate the anti-inflammatory role of dihydrotestosterone (DHT) in high glucose (HG)-induced neuroinflammatory response in BV-2 microglia. Our results revealed that DHT significantly inhibited HG-induced production of nitric oxide and prostaglandin E2 through suppressing the expression of corresponding regulatory enzymes – inducible NO synthase and cyclooxygenase-2. Also, DHT inhibited HG-induced expression of TNF-α and IL-1β. Moreover, DHT suppressed the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, when SH-SY5Y neurons were cultured in HG-treated BV-2 microglial supernatant, DHT pretreatment significantly increased neuronal survival, indicating the neuroprotective role of DHT. Collectively, these results suggest that DHT could protect SH-SY5Y neurons from HG-mediated BV-2 microglia inflammatory damage through inhibiting TLR4/NF-κB signaling, suggesting that maintenance of androgen level in brain might have potential benefit in neurodegenerative diseases, especially in diabetes patients combined with cognitive disorders.

Source: NeuroReport - January 15, 2020 Category: Neurology Tags: Degeneration and Repair Source Type: research