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Hokkaido University Collection of Scholarly and Academic Papers >
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Accumulation of Senescent Neural Cells in Murine Lupus With Depression-Like Behavior
| Title: | Accumulation of Senescent Neural Cells in Murine Lupus With Depression-Like Behavior |
| Authors: | Saito, Yuki Browse this author →KAKEN DB | | Miyajima, Maki Browse this author →KAKEN DB | | Yamamoto, Sena Browse this author | | Sato, Tsukasa Browse this author | | Miura, Norihiro Browse this author | | Fujimiya, Mineko Browse this author | | Chikenji, Takako S. Browse this author →KAKEN DB |
| Keywords: | systemic lupus erythematosus | | senescence | | depression | | inflammation | | SASP (senescence-associated secretory phenotype) |
| Issue Date: | 3-Nov-2021 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in immunology |
| Volume: | 12 |
| Start Page: | 692321 |
| Publisher DOI: | 10.3389/fimmu.2021.692321 |
| Abstract: | Neuropsychiatric 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/83705 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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