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    題名: STAT1 negatively regulates spatial memory formation and mediates the memory-impairing effect of Aβ
    作者: Hsu, Wei-Lun
    Ma, Yun-Li
    Hsieh, Ding-You
    Liu, Yen-Chen
    Lee, Eminy HY
    貢獻者: 神科所
    關鍵詞: STAT1;LB1;CREB;amyloid-beta;NMDA receptor subunit;spatial learning and memory
    日期: 2014-02
    上傳時間: 2017-08-15 17:00:41 (UTC+8)
    摘要: Signal transducer and activator of transcription-1 (STAT1) has an important role in inflammation and the innate immune response, but its role in the central nervous system is less well understood. Here, we examined the role of STAT1 in spatial learning and memory, and assessed the involvement of STAT1 in mediating the memory-impairing effect of amyloid-beta (Aβ). We found that water maze training downregulated STAT1 expression in the rat hippocampal CA1 area, and spatial learning and memory function was enhanced in Stat1-knockout mice. Conversely, overexpression of STAT1 impaired water maze performance. STAT1 strongly upregulated the expression of the extracellular matrix protein laminin β1 (LB1), which also impaired water maze performance in rats. Furthermore, Aβ impaired spatial learning and memory in association with a dose-dependent increase in STAT1 and LB1 expression, but knockdown of STAT1 and LB1 both reversed this effect of Aβ. This Aβ-induced increase in STAT1 and LB1 expression was also associated with a decrease in the expression of the N-methyl-D-aspartate receptor (NMDAR) subunits, NR1, and NR2B. Overexpression of NR1 or NR2B or exogenous application of NMDA reversed Aβ-induced learning and memory deficits as well as Aβ-induced STAT1 and LB1 expression. Our results demonstrate that STAT1 negatively regulates spatial learning and memory through transcriptional regulation of LB1 expression. We also identified a novel mechanism for Aβ pathogenesis through STAT1 induction. Notably, impairment of spatial learning and memory by this STAT1-mediated mechanism is independent of cAMP responsive element-binding protein signaling. © 2014 American College of Neuropsychopharmacology.
    關聯: Neuropsychopharmacology, 39(3), 746-758
    資料類型: article
    DOI 連結: http://dx.doi.org/10.1038/npp.2013.263
    DOI: 10.1038/npp.2013.263
    顯示於類別:[神經科學研究所 ] 期刊論文

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