Hippocampal ornithine decarboxylase/spermidine pathway mediates H2S-alleviated cognitive impairment in diabetic rats: Involving enhancment of hippocampal autophagic flux

Xuan Kang; Cheng Li; Yan Xie; Ling-Li He; Fan Xiao; Ke-Bin Zhan; Yi-Yun Tang; Xiang Li; Xiao-Qing Tang

Journal of Advanced Research (Jan 2021)

Hippocampal ornithine decarboxylase/spermidine pathway mediates H2S-alleviated cognitive impairment in diabetic rats: Involving enhancment of hippocampal autophagic flux

Xuan Kang,
Cheng Li,
Yan Xie,
Ling-Li He,
Fan Xiao,
Ke-Bin Zhan,
Yi-Yun Tang,
Xiang Li,
Xiao-Qing Tang

Affiliations

Xuan Kang: Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, PR China
Cheng Li: Department of Emergency Affiliated Nanhua Hospital, University of South China, Hengyang 421001, Hunan, PR China; Department of Neurology, The Second Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China
Yan Xie: Department of Neurology, The Second Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China
Ling-Li He: Department of Neurology, The Second Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China
Fan Xiao: Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, PR China
Ke-Bin Zhan: Department of Neurology, The Second Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China; Corresponding authorsat: Institute of neurology, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang 421001, Hunan, PR China (Xiao-Qing Tang), Department of Neurology, The Second Affiliated Hospital, University of South China, 35 Jiefang Road, Hengyang 421001, Hunan, PR China (Ke-Bin Zhan).
Yi-Yun Tang: Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, PR China
Xiang Li: Department of Anesthesiology, The First Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China
Xiao-Qing Tang: Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, PR China; Corresponding authorsat: Institute of neurology, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang 421001, Hunan, PR China (Xiao-Qing Tang), Department of Neurology, The Second Affiliated Hospital, University of South China, 35 Jiefang Road, Hengyang 421001, Hunan, PR China (Ke-Bin Zhan).

Journal volume & issue: Vol. 27
pp. 31 – 40

Abstract

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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.

Published in Journal of Advanced Research

ISSN: 2090-1232 (Print); 2090-1224 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Science (General)
Website: http://www.journals.elsevier.com/journal-of-advanced-research/

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