Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2019 Volume 20 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2019 Volume 20 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia

  • Authors:
    • Xia Guo
    • Yao Liu
    • Yaning Zhao
    • Rong Fan
    • Yali Bai
    • Xiangfei Guo
    • Jianmin Li
    • Changxiang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Rehabilitation, College of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China
  • Pages: 1411-1417
    |
    Published online on: June 4, 2019
       https://doi.org/10.3892/mmr.2019.10337
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study aimed to compare the expression of phosphatidylinositol 3‑kinase (PI3‑K), mammalian target of rapamycin (mTOR) and Beclin‑1 between the hippocampi of normal rats and intermittent ischemic rats following whole brain ischemia/reperfusion (I/R), and investigate the role of the PI3K‑mTOR autophagy pathway in rat nerve damage following intermittent hypoxia (IH)‑aggravated whole brain ischemia. A total of 80 male Wistar rats were divided by random number table into a sham operation group (SO group; 20 rats), pure cerebral ischemia/reperfusion group (I/R group; 20 rats), intermittent hypoxia for 7 days‑I/R group (IH7+I/R group; 20 rats) and intermittent hypoxia for 21 days‑IR group (IH21+I/R group; 20 rats). Prior to model establishment, the rats in the IH7+I/R group and IH21+I/R group underwent intermittent hypoxia for 7 and 21 days, respectively. The optimized Pulsinelli 4‑vessel occlusion method was used to prepare the I/R model. H&E staining and transmission electron microscopy were performed to observe the morphological changes of nerve cells in the hippocampus. Immunohistochemical and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses were performed to detect the expression levels of PI3‑K, mTOR and Beclin‑1 in the hippocampal brain tissues of the rats. A Morris water maze test was used to assess rat learning and memory. The results showed that, compared with the SO group, the rats in the I/R group exhibited structural damage in neurons (shown by H&E staining), a reduced number of viable nerve cells, and decreased learning and memory ability at each time point. The results of the immunohistochemical analysis showed that the numbers of PI3‑K, mTOR and Beclin‑1 immunopositive cells were increased (P<0.05). The RT‑qPCR analysis showed increased expression levels of PI3‑K, mTOR and Beclin‑1 (P<0.05). Compared with the I/R group, the rats in the IH‑I/R groups exhibited aggravated structural damage in neurons, shown by H&E staining and electron microscopy. The number of viable nerve cells was decreased, and the rats exhibited decreased learning ability and memory. The immunohistochemical analysis revealed that the numbers of PI3‑K, mTOR and Beclin‑1 immunopositive cells were increased (P<0.05). The RT‑qPCR analysis showed increased expression levels of PI3‑K, mTOR and Beclin‑1 (P<0.05). The above changes were more marked in the IH21+I/R group (P<0.05). Taken together, IH was shown to aggravate nerve damage following whole brain I/R. The underlying mechanism was associated with activation of the PI3K‑mTOR‑autophagy pathway and increased loss of nerve cells.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Deng XZ, Liu B and Li Y: Research progress of obstructive sleep apnea hyponea syndrome and hypertension. Adv Cardiovasc Dis. 35:230–233. 2014.(In Chinese).

2 

Cho ER, Kim H, Seo HS, Suh S, Lee SK and Shin C: Obstructive sleep apnea as a risk factor for silent cerebral infarction. J Sleep Res. 22:452–458. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Wang Z, Zhao YN and Li JM: Effects of grape seed proanthocyanidin extract on peroxidation and ability of learning and memory after cerebral ischemia/re-perfusion injury in rats. Chin J Rehabil Theory Pract. 20:827–830. 2014.(In Chinese).

4 

Tang YA: Study on cognitive impairment and mechanism causing by chronic cerebral hypoperfusion in rats. Sichuan Med J. 31:1226–1228. 2010.(In Chinese).

5 

Wang WY, Cui ZR and Jiang W: Autophagy in research progress in the role of brain ischemia-reperfusion injury. J Shanghai Jiaotong Univ. 34:248–253. 2014.(In Chinese).

6 

Sami A and Karsy M: Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: Novel therapeutic agents and advances in understanding. Tumour Biol. 34:1991–2002. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Jeong EH, Choi HS, Lee TG, Kim HR and Kim CH: Dual inhibition of PI3K/Akt/mTOR pathway and role of autophagy in non-small cell lung cancer cells. Tuberc Respir Dis (Seoul). 72:343–351. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Bin Y, Yu LJ, Wang J, Zhao L, Hu XY, Ji CN, Wei YL, Yang QF, Jiang QS, Yang JQ, et al: Time course change of PGI2 and TA2 levels in rat cortex following global cerebral ischemia reperfusion. Chin Pharmacol Bull. 29:1667–1671. 2013.(In Chinese).

9 

Capampangan DJ, Wellik KE, Parish JM, Aguilar MI, Snyder CR, Wingerchuk D and Demaerschalk BM: Is obstructive sleep apnea an independent risk factor for stroke? A critically appraised topic. Neurologist. 16:269–273. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Guo X, Zhao Y, Li J, Liu W and Chen C: Activation of autophagy pathway in hippocampus and deterioration of learning and memory ability by intermittent hypoxia in rats after cerebral ischemia. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 32:1212–1216. 2016.(In Chinese). PubMed/NCBI

11 

Yang D and Liu ZH: Exploring the relationship and pathogenesis between obstructive sleep apnea and cardiovascular diseases. Adv Cardiovasc Dis. 32:645–648. 2011.(In Chinese).

12 

Sun ZM, Zhao YN, Li JM, Chen CX, Zhao X and Chen NL: Effect of intensity of exercise on learning ability and oxygen free radical metabolism in rats after cerebral ischemia-reperfu-sion. Chin J Rehabil Theory Pract. 21:26–30. 2015.(In Chinese).

13 

Lu WL, Guo Y, Li DX and Zhang S: Effects of obstructive sleep apnea syndrome on cognitive function in ischemic stroke patients. Chinese Community Doctors,. 30:26–27. 2014.(In Chinese).

14 

Mansukhani MP, Bellolio MF, Kolla BP, Enduri S, Somers VK and Stead LG: Worse outcome after stroke in patients with obstructive sleep apnea: An observational cohort study. J Stroke Cerebrovasc Dis. 20:401–405. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Ding H, Tang YH and Huang XP: Effects of autophagy in cerebral ischemic injury. Chin Pharmacol Bull. 31:1048–1052. 2015.(In Chinese).

16 

Wang JY, Xia Q, Chu KT, Pan J, Sun LN, Zeng B, Zhu YJ, Wang Q, Wang K and Luo BY: Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in mt is prevented by 3-Methyladenine: A widely used inhibitor of autophagy. J Neuropathol Exp Neurol. 70:314–322. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Liu HY, Chen R, Li YN, Zhang YL and Liu CF: Chronic intermittent hypoxia area in mice hippocampal CAl neurons autophagy. Chin J Tuberc Respir Dis. 34:467–469. 2011.(In Chinese).

18 

Wu MM, Wan RH and Chen NH: Research progress on the mTOR signaling pathway and neurodegenerative disease. Chin Pharmacol Bull. 27:1481–1483. 2011.(In Chinese).

19 

Ishrat T, Sayeed I, Atif F, Hua F and Stein DG: Progesterone is neuroprotective against ischemic brain injury through its effects on the phosphoinositide 3-kinase/protein kinase B signaling pathway. Neuroscience. 210:442–450. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Zhao L, Zhang XH, Wu BC, et al: Hawthorn leaves flavonoids on cerebral ischemia rats organization PI3K/Akt signal pathway. Guangdong Med J. 35:982–984. 2014.(In Chinese).

21 

Sengupta S, Peterson TR and Sabatini DM: Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 40:310–322. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Liu L and Xu PC: Sevoflurane pretreatment of rats in vitro cardiac ischemia-reperfusion injury when autophagy and the effect of PI3K/Akt signaling pathway in the role. Chin J Anesthesiol. 34:492–496. 2014.

23 

Gong L, Wang Z, Xing YG, et al: Effects of ischemic postconditioning on apoptosis in cerebral ischemia-reperfusion injury in rats and its mechanisms. J Int Neurol Neurosurg. 39:229–234. 2012.

24 

Yang ML and Cai RW: Inflammatory reaction in obstructive sleep apnea syndrome and ischemic strok. Med Recapitul. 16:919–921. 2010.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Guo X, Liu Y, Zhao Y, Fan R, Bai Y, Guo X, Li J and Chen C: Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia. Mol Med Rep 20: 1411-1417, 2019.
APA
Guo, X., Liu, Y., Zhao, Y., Fan, R., Bai, Y., Guo, X. ... Chen, C. (2019). Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia. Molecular Medicine Reports, 20, 1411-1417. https://doi.org/10.3892/mmr.2019.10337
MLA
Guo, X., Liu, Y., Zhao, Y., Fan, R., Bai, Y., Guo, X., Li, J., Chen, C."Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia". Molecular Medicine Reports 20.2 (2019): 1411-1417.
Chicago
Guo, X., Liu, Y., Zhao, Y., Fan, R., Bai, Y., Guo, X., Li, J., Chen, C."Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia". Molecular Medicine Reports 20, no. 2 (2019): 1411-1417. https://doi.org/10.3892/mmr.2019.10337
Copy and paste a formatted citation
x
Spandidos Publications style
Guo X, Liu Y, Zhao Y, Fan R, Bai Y, Guo X, Li J and Chen C: Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia. Mol Med Rep 20: 1411-1417, 2019.
APA
Guo, X., Liu, Y., Zhao, Y., Fan, R., Bai, Y., Guo, X. ... Chen, C. (2019). Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia. Molecular Medicine Reports, 20, 1411-1417. https://doi.org/10.3892/mmr.2019.10337
MLA
Guo, X., Liu, Y., Zhao, Y., Fan, R., Bai, Y., Guo, X., Li, J., Chen, C."Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia". Molecular Medicine Reports 20.2 (2019): 1411-1417.
Chicago
Guo, X., Liu, Y., Zhao, Y., Fan, R., Bai, Y., Guo, X., Li, J., Chen, C."Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent hypoxia‑aggravated whole brain ischemia". Molecular Medicine Reports 20, no. 2 (2019): 1411-1417. https://doi.org/10.3892/mmr.2019.10337
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team