烟酰胺-姜黄素通过挽救 CA1 海马体中的自噬流来改善糖尿病大鼠的认知障碍。
Nicotinate-curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus.
机构信息
Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, China.
Department of Endocrine of the Second Affiliated Hospital, University of South China, Hengyang, China.
出版信息
CNS Neurosci Ther. 2019 Apr;25(4):430-441. doi: 10.1111/cns.13059. Epub 2018 Sep 9.
INTRODUCTION
Our previous study has confirmed that a novel curcumin derivate nicotinate-curcumin (NC) can facilitate autophagic flux in THP-1 cells induced by oxidized low-density lipoprotein.
AIMS
Given that autophagy plays critical roles in neurodegenerative diseases, the present study was carried out to investigate whether NC can improve cognitive function of rats with diabetes mellitus (DM) via restoring autophagic flux in CA1 hippocampus.
RESULTS
Our results showed that NC treatment improved cognitive deficit and attenuated neuronal loss as well as cellular ultrastructure impairment in the CA1 region of DM rats induced by streptozotocin. Moreover, NC lowered the expressions of the apoptosis-related proteins Bcl-2, Bax, Cyt-c, and cleaved Caspase-3. Notably, NC treatment reversed autophagic flux impairment as evidenced by the deceases in LC3-II and p62 protein levels, and autophagosome accumulation in the hippocampal CA1 region of DM rats. However, these protective effects of NC were abolished by cotreatment with 3-methyladenine (an autophagy inhibitor) and chloroquine (an autophagic flux inhibitor), respectively. Furthermore, NC treatment decreased the expressions of phosphorylated mammalian target of rapamycin (mTOR) and p70 ribosomal protein S6 kinase (p70S6k) proteins in the CA1 region of DM rats.
CONCLUSIONS
These results indicate that NC ameliorates DM-induced cognitive function impairment via restoring autophagic flux might by inhibiting mTOR/p70S6k activation in the CA1 region, and NC may be a promising agent for diabetic cognitive dysfunction prevention and treatment.
简介
我们之前的研究已经证实，一种新型姜黄素衍生物烟酸盐-姜黄素（NC）可以促进氧化型低密度脂蛋白诱导的 THP-1 细胞自噬流。
目的
鉴于自噬在神经退行性疾病中起着关键作用，本研究旨在探讨 NC 是否可以通过恢复糖尿病大鼠 CA1 海马中的自噬流来改善其认知功能。
结果
我们的结果表明，NC 治疗改善了糖尿病大鼠认知功能障碍，并减轻了神经元丢失和细胞超微结构损伤，这些损伤是由链脲佐菌素诱导的。此外，NC 降低了凋亡相关蛋白 Bcl-2、Bax、Cyt-c 和 cleaved Caspase-3 的表达。值得注意的是，NC 治疗逆转了自噬流损伤，这表现在 LC3-II 和 p62 蛋白水平的降低，以及糖尿病大鼠海马 CA1 区自噬体的积累。然而，这些 NC 的保护作用被 3-甲基腺嘌呤（自噬抑制剂）和氯喹（自噬流抑制剂）的共同处理分别消除。此外，NC 治疗降低了糖尿病大鼠 CA1 区磷酸化哺乳动物雷帕霉素靶蛋白（mTOR）和 p70 核糖体蛋白 S6 激酶（p70S6k）蛋白的表达。
结论
这些结果表明，NC 通过恢复自噬流改善糖尿病引起的认知功能障碍，可能是通过抑制 CA1 区的 mTOR/p70S6k 激活，NC 可能是预防和治疗糖尿病认知功能障碍的有前途的药物。
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