|a英文題名:Effects of Rhodiola Crenulata on Learning and Memory in SAMP8 Mice by Sirtuin-1 Mediation
|a自噬(Autophagy)具協助細胞生長、分化及代謝受損胞器的功能。隨著年齡的增長細胞凋亡(Apoptosis)隨之上升而自噬則會下降，且可能與自體免疫及神經變性等疾病有關。研究指出紅景天屬植物(Rhodiola plant)具有抗氧化、抗發炎與神經保護等效果，不過是否可調節自噬作用的能力則鮮少被探討，本研究目的為探討老化促進小鼠(SAMP8 mice)給予大花紅景天(Rhodiola crenulata, RC)後經自噬作用相關蛋白中Sirt-1調控之相關機制與影響。實驗選用三月齡SAMP8雄性小鼠，分為控制組、低(100 mg/Kg BW)、中(200 mg/Kg BW)與高(400 mg/Kg BW)劑量RC水萃物組，自由飲水與攝食，每週記錄體重及攝食量，於第十一週進行活動量測試，第十二週以單次被動試驗及主動迴避試驗評估學習記憶能力，並於第十三週犧牲。結果顯示，RC可改善主、被動之學習記憶能力試驗，降低APP蛋白質表現量，且減少腦中Aβ1-42沉積；此外，可提升自噬相關蛋白Sirt-1、LC3B、Beclin-1和神經保護因子BDNF及其轉錄因子p-CREB蛋白質之表現量，抑制細胞凋亡相關蛋白p-mTOR及下游p-P70S6K之表現。由以上推論，RC因為可促進Sirt-1，可能因此活化自噬作用以及p-CREB並轉錄BDNF，減少活化mTOR、P70S6K，減少APP之表現，減少Aβ1-42沉積，達到神經保護功能進而改善學習記憶之能力。綜合以上證實RC可藉由調節Sirt-1以達到神經保護的效果。|uAutophagy could assist cell growth, differentiation and metabolism of damaged organelles. Aoptosis also increased with aging where the autophagy decreased, both of them may be related to autoimmune and neurodegenerative diseases. Studies had proved that Rhodiola plant had benifical effects on antioxidant, anti-inflammation and neuroprotection, but the influence on autophagy is rarely discussed. This study aimed to evaluate the effects of Rhodiola crenulata (RC) on the autophagy-related proteins with senescence accelerated mouse prone 8 (SAMP8) mice. 3-month-old SAMP8 male mice were divided into control, low (100 mg/kg), medium (200 mg/kg) and high (400 mg/kg) RC groups and fed for 12 weeks. Weight and food intake were checked weekly. The locomotion was test in the 11th week, and the single passive test and active avoidance test were used to assess the ability of learning and memory in the 12th week. The results showed RC could improve active and passive avoidance performances, and decreased the APP protein expression and Aβ1-42 accumulation in the brain. The autophagy-related proteins Sirt-1, LC3B, Beclin-1 and neuroprotection factor-BDNF and it’s transcription factor p-CREB protein increased in RC groups. Moreover, RC could inhibite the apoptosis related protein p-mTOR and downstream p-P70S6K protein expressions. In summary, RC showed to promote Sirt-1, which might activate autophagy and p-CREB and transcription of BDNF, reduced the activation of mTOR, P70S6K, decreased the APP and Aβ1-42 deposition, and then improve neurological protection and the learning and memory abilities. With the above, our results suggested that RC achieved the neuroprotection by regulating Sirt-1.
|aEffects of Rhodiola Crenulata on Learning and Memory in SAMP8 Mice by Sirtuin-1 Mediation