2024-03-28T20:04:19Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/837052022-11-17T02:08:08Zhdl_2115_35410hdl_2115_35409Accumulation of Senescent Neural Cells in Murine Lupus With Depression-Like BehaviorSaito, YukiMiyajima, MakiYamamoto, SenaSato, TsukasaMiura, NorihiroFujimiya, MinekoChikenji, Takako S.systemic lupus erythematosussenescencedepressioninflammationSASP (senescence-associated secretory phenotype)490Neuropsychiatric manifestations targeting the central, peripheral, and autonomic nervous system are common in systemic lupus erythematosus (SLE); collectively, these symptoms are termed neuropsychiatric SLE (NPSLE). Among a wide variety of neuropsychiatric symptoms, depression is observed in about 24-39% of SLE patients. Several cytokines and chemokines have been identified as biomarkers or therapeutic targets of NPSLE; in particular, the levels of type 1 interferons, TNFs, and IL-6 are elevated in SLE patient's cerebrospinal fluid (CSF), and these factors contribute to the pathology of depression. Here, we show that senescent neural cells accumulate in the hippocampal cornu ammonis 3 (CA3) region in MRL/lpr SLE model mice with depressive behavior. Furthermore, oral administration of fisetin, a senolytic drug, reduced the number of senescent neural cells and reduced depressive behavior in the MRL/lpr mice. In addition, transcription of several senescence and senescence-associated secretory phenotype (SASP) factors in the hippocampal region also decreased after fisetin treatment in the MRL/lpr mice. These results indicate that the accumulation of senescent neural cells in the hippocampus plays a role in NPSLE pathogenesis, and therapies targeting senescent cells may represent a candidate approach to treat NPSLE.Frontiers MediaJournal Articlehttp://hdl.handle.net/2115/837051664-3224Frontiers in immunology126923212021-11-03enginfo:doi/10.3389/fimmu.2021.692321none