当前位置: X-MOL 学术J. Adv. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Hippocampal ornithine decarboxylase/spermidine pathway mediates H2S-alleviated cognitive impairment in diabetic rats: Involving enhancment of hippocampal autophagic flux
Journal of Advanced Research ( IF 10.7 ) Pub Date : 2020-06-12 , DOI: 10.1016/j.jare.2020.06.007
Xuan Kang 1, 2 , Cheng Li 3, 4 , Yan Xie 4 , Ling-Li He 4 , Fan Xiao 2 , Ke-Bin Zhan 4 , Yi-Yun Tang 2 , Xiang Li 5 , Xiao-Qing Tang 1, 2
Affiliation  

Introduction

We have previously demonstrated the antagonistic role of hydrogen sulfide (H2S) in the cognitive dysfunction of streptozotocin (STZ)-induced diabetic rats. It has been confirmed that the impaired hippocampal autophagic flux has a key role in the pathogenesis of cognitive impairment and that ornithine decarboxylase (ODC)/spermidine (Spd) pathway plays an important role in the formation of memory by promoting autophagic flux.

Objectives

To investigate the roles of hippocampal ODC/Spd pathway and autophagic flux in H2S-attenuated cognitive impairment in STZ-induced diabetic rats.

Methods

Cognitive function is judged by the novel objective recognition task (NOR), the Y-maze, and the Morris water maze (MWM) tests. The ODC/Spd pathway in hippocampus was evaluated using the expression of ODC detected by western blot and the level of Spd assayed by GC-MS. Autophagic flux was assessed using the expressions of Beclin-1, LC3II/I, and P62 detected by western blot, and the number of autophagosomes observed by transmission electron microscope.

Results

Sodium hydrosulfide (NaHS, a donor of H2S) markedly improved the autophagic flux in the hippocampus of STZ-exposed rats, as evidenced by a decrease in the number of autophagosomes as wells as downregulations in the expressions of LC3-II, Beclin-1, and P62 in the hippocampus of cotreatment with NaHS and STZ rats. NaHS also up-regulated the expression of ODC and the level of Spd in the hippocampus of STZ-induced diabetic rats. Furthermore, inhibited hippocampal ODC/Spd pathway by difluoromethylornithine (DFMO) markedly reversed the protections of NaHS against the hippocampal autophagic flux impairment as well as the cognitive dysfunction in STZ-exposed rats.

Conclusion

These findings indicated that improving hippocampal autophagic flux plays a key role in H2S-attenuated cognitive impairment in STZ-induced diabetic rats, as results of up-regulating hippocampal ODC/Spd pathway.



中文翻译:

海马鸟氨酸脱羧酶/亚精胺通路介导 H2S 减轻糖尿病大鼠认知障碍:涉及海马自噬通量的增强

介绍

我们之前已经证明了硫化氢 (H2S) 在链脲佐菌素 (STZ) 诱导的糖尿病大鼠认知功能障碍中的拮抗作用。已证实海马自噬流受损在认知障碍的发病机制中起关键作用,鸟氨酸脱羧酶(ODC)/亚精胺(Spd)通路通过促进自噬流在记忆形成中起重要作用。

目标

探讨海马 ODC/Spd 通路和自噬通量在 STZ 诱导的糖尿病大鼠 H2S 减弱认知障碍中的作用。

方法

认知功能通过新颖的客观识别任务 (NOR)、Y 迷宫和莫里斯水迷宫 (MWM) 测试来判断。使用western blot检测ODC表达和GC-MS检测Spd水平评估海马ODC/Spd通路。采用western blot检测Beclin-1、LC3II/I和P62的表达,透射电镜观察自噬体数量,评估自噬通量。

结果

硫氢化钠(NaHS,H2S 的供体)显着改善 STZ 暴露大鼠海马中的自噬通量,这可以通过自噬体数量减少以及 LC3-II、Beclin-1、与 NaHS 和 STZ 大鼠共同治疗的海马中的 P62 和 P62。NaHS还上调STZ诱导的糖尿病大鼠海马ODC的表达和Spd的水平。此外,二氟甲基鸟氨酸 (DFMO) 抑制海马 ODC/Spd 通路显着逆转了 NaHS 对 STZ 暴露大鼠海马自噬通量损伤和认知功能障碍的保护作用。

结论

这些发现表明,改善海马自噬通量在 STZ 诱导的糖尿病大鼠 H2S 减弱的认知障碍中起关键作用,这是上调海马 ODC/Spd 通路的结果。

更新日期:2020-06-12
down
wechat
bug