Hippocampal ornithine decarboxylase/spermidine pathway mediates H(2)S-alleviated cognitive impairment in diabetic rats: Involving enhancment of hippocampal autophagic flux.
Hippocampal ornithine decarboxylase/spermidine pathway mediates H(2)S-alleviated cognitive impairment in diabetic rats: Involving enhancment of hippocampal autophagic flux.
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海马鸟氨酸脱羧酶/亚精胺通路介导糖尿病大鼠 H2S 缓解的认知障碍：涉及海马自噬通量的增强
DOI：
10.1016/j.jare.2020.06.007
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发表时间：
2021-01
影响因子：
10.7
通讯作者：
Tang XQ
中科院分区：
文献类型：
--
作者：
Kang X;Li C;Xie Y;He LL;Xiao F;Zhan KB;Tang YY;Li X;Tang XQ
我们先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。研究证实，海马自噬通量受损在认知功能障碍的发病机制中起关键作用，而鸟氨酸脱羧酶（ODC）/亚精胺（Spd）通路通过促进自噬通量在记忆形成中起重要作用。探讨海马ODC/Spd通路和自噬通量在H2S致糖尿病大鼠认知功能损害中的作用。认知功能通过新的客观识别任务（NOR）、Y-迷宫和Morris水迷宫（MWM）测试来判断。Western blot检测海马ODC表达，GC-MS检测Spd水平，Western blot检测Beclin-1、LC 3 II/I、P62蛋白表达，透射电镜观察自噬体数量。硫氢化钠（NaHS，H2S的供体）显著改善STZ暴露大鼠海马中的自噬通量，如自噬体数量的减少和LC 3-II、Beclin-1和P62在NaHS和STZ共处理大鼠海马中表达的下调所证明的威尔斯。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通路可明显逆转NaHS对STZ暴露大鼠海马自噬通量损害和认知功能障碍的保护作用。这些结果表明，提高海马自噬流量在STZ诱导的糖尿病大鼠H2S减轻认知障碍中起关键作用，是上调海马ODC/Spd通路的结果。
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. To investigate the roles of hippocampal ODC/Spd pathway and autophagic flux in H2S-attenuated cognitive impairment in STZ-induced diabetic rats. 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. 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. 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.
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