Cognitive Protective Mechanism of Crocin Pretreatment in Rat Submitted to Acute High-Altitude Hypoxia Exposure.

Inadequate oxygen availability at high altitude leads to oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. In our previous study, we found that the cognitive dysfunction occurred when male SD rat was rapidly exposed to 4200 m of high altitude for 3 days. And we also...

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Publicado en:BioMed Research International pp. 1 - 16
Autores principales: Zhang, Xiaoyan, Zhang, Xianjun, Dang, Zhancui, Su, Shanshan, Li, Zhanqiang, Lu, Dianxiang
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 6/10/2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 6/10/2020
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2020/3409679
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        atl: Cognitive Protective Mechanism of Crocin Pretreatment in Rat Submitted to Acute High-Altitude Hypoxia Exposure.
      aug:
        au:
          Zhang, Xiaoyan
          Zhang, Xianjun
          Dang, Zhancui
          Su, Shanshan
          Li, Zhanqiang
          Lu, Dianxiang
        affil: Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine, Ministry of Education, Qinghai University, Xining 810001, China
      sug:
        subj:
          Carotenoids Pharmacodynamics
          Transferases Drug Effects
          Peroxisome Proliferator-Activated Receptors Drug Effects
          Signal Transduction Drug Effects
          Hippocampus Drug Effects
          Cognition Drug Effects
          Altitude Sickness
          Anoxia
          Animal Studies
          Rats
          Molecular Structure
          Learning Drug Effects
          Memory Drug Effects
          Staining and Labeling Methods
          DNA-Binding Proteins Drug Effects
          Gene Expression Drug Effects
          Caspases Drug Effects
          Oncogenes Drug Effects
          Immunohistochemistry
          Polymerase Chain Reaction Methods
          Blotting, Western
          Malondialdehyde Drug Effects
          Superoxide Dismutase Drug Effects
          Glutathione Drug Effects
          Glutathione Peroxidase Drug Effects
          Colorimetry
          Neurons Drug Effects
          Apoptosis Drug Effects
      ab: Inadequate oxygen availability at high altitude leads to oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. In our previous study, we found that the cognitive dysfunction occurred when male SD rat was rapidly exposed to 4200 m of high altitude for 3 days. And we also found that crocin showed a cognitive protective effect under hypoxia by regulating SIRT1/PGC-1α pathways in rat's hippocampus. In this article, focused on factors related to SIRT1/PGC-1α pathways, we proposed to further elucidate crocin's pharmacological mechanism. Adult male Sprague-Dawley rats were randomly divided into five groups: control group, hypoxia group (rats were rapidly transported to high altitude of 4200 m for 72 h), and crocins+hypoxia groups (pretreatment with crocin of 25, 50, and 100 mg/kg/d for 3 days). The learning and memory ability was tested by Morris water maze analysis. Hippocampal histopathological changes were observed by HE staining and Nissl staining. The expression of NRF1, TFAM, Bcl-2, Bax, and caspase-3 was detected by immunohistochemistry, RT-PCR, and western blotting test. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSHPx) were detected by the TBA, WST, and colorimetry method. Neuronal apoptosis was observed by TUNEL staining. After crocin pretreatment, the traveled distance was significantly reduced and the percentage of time in the target quadrant was significantly increased tested by Morris water maze. And neuronal damage in the hippocampus was also significantly ameliorated based on HE staining and Nissl staining. Furthermore, in hippocampus tissue, mitochondrial biosynthesis-related factors of NRF1, TFAM expression was increased; oxidative stress factors of SOD, GSH, and GSHPx expression level were increased, and MDA and glutathione disulfide (GSSG) level were decreased; antiapoptotic protein Bcl-2 expression was increased, and proapoptotic proteins Bax and caspase-3 expression were decreased, with a manner of crocin dose dependent. Therefore, the cognitive protective mechanism of crocin in rat under acute hypoxia was related to promoting mitochondrial biosynthesis, ameliorating oxidative stress injury, and decreasing neuronal apoptosis.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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