The SIRT1-HMGB1 pathway in hippocampal microglia is involved in chronic heroin-induced cognitive impairment.

Recent studies have found that microglia-mediated hippocampal damage may be involved in cognitive impairment induced by chronic heroin treatment. However, its specific molecular mechanism remains unclear. This study explored the possible role of the SIRT1-HMGB1 pathway in this phenomenon. We found that 30 days, but not 15 days, of chronic heroin treatment could impair the learning and memory of mice in the water maze task; compared with 15 days of heroin treatment, 30 days of chronic heroin treatment induced more hippocampal SIRT1 and HMGB1 expression, especially the number of SIRT1-positive and HMGB1-positive microglia, and promoted the polarization of microglia to proinflammatory types. Selective knockdown of SIRT1 expression in hippocampal microglia exacerbated the learning and memory impairment induced by 30 days of heroin treatment; reduced the number of HMGB1-positive microglia, reversed the polarization of microglia to proinflammatory types, and exacerbated the apoptosis of cells in the hippocampus. These results suggest that chronic heroin treatment may be involved in the cognitive impairment process by activating the SIRT1-HMGB1 pathway in microglia.