Advertisement

Cellular and Molecular Neurobiology

, Volume 36, Issue 5, pp 821–828 | Cite as

Ischemia-Induced Changes of PRAS40 and p-PRAS40 Immunoreactivities in the Gerbil Hippocampal CA1 Region After Transient Cerebral Ischemia

  • Joon Ha Park
  • Bich Na Shin
  • Ji Hyeon Ahn
  • Jeong-Hwi Cho
  • In Hye Kim
  • Dae Won Kim
  • Moo-Ho Won
  • Seongkweon Hong
  • Jun Hwi ChoEmail author
  • Choong-Hyun LeeEmail author
Original Research

Abstract

Proline-rich Akt substrate of 40-kDa (PRAS40) is one of the important interactive linkers between Akt and mTOR signaling pathways. The increase of PRAS40 is related with the reduction of brain damage induced by cerebral ischemia. In the present study, we investigated time-dependent changes in PRAS40 and phospho-PRAS40 (p-PRAS40) immunoreactivities in the hippocampal CA1 region of the gerbil after 5 min of transient cerebral ischemia. PRAS40 immunoreactivity in the CA1 region was decreased in pyramidal neurons from 12 h after ischemic insult in a time-dependent manner, and, at 5 days post-ischemia, PRAS40 immunoreactivity was newly expressed in astrocytes. p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was hardly found 12 h and apparently detected again 1 and 2 days after ischemic insult. At 5 days post-ischemia, p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was not found. These results indicate that ischemia-induced changes in PRAS40 and p-PRAS40 immunoreactivities in CA1 pyramidal neurons and astrocytes may be closely associated with delayed neuronal death in the hippocampal CA1 region following transient cerebral ischemia.

Keywords

PRAS40 Transient global cerebral ischemia Delayed neuronal death Astrocyte 

Notes

Acknowledgments

The authors would like to thank Mr. Seung Uk Lee for technical help. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A1A2058440), by a Grant HO14C0001 from Osong Innovation Center funded by the Ministry of Health & Welfare, the Republic of Korea, and by 2013 Research Grant from Kangwon National University (No. 120131326).

Compliance with Ethical Standards

Disclosure of potential conflicts of interest

The authors declare that they have no potential conflicts of interest.

Statement on the welfare of animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

References

  1. Chan PH (2004) Future targets and cascades for neuroprotective strategies. Stroke 35(11 Suppl 1):2748–2750CrossRefPubMedGoogle Scholar
  2. Dai J, Chen L, Qiu YM et al (2013) Activations of GABAergic signaling, HSP70 and MAPK cascades are involved in baicalin’s neuroprotection against gerbil global ischemia/reperfusion injury. Brain Res Bull 90:1–9CrossRefPubMedGoogle Scholar
  3. Davis CM, Fairbanks SL, Alkayed NJ (2013) Mechanism of the sex difference in endothelial dysfunction after stroke. Transl Stroke Res 4(4):381–389CrossRefPubMedGoogle Scholar
  4. Gamdzyk M, Makarewicz D, Slomka M et al (2014) Hypobaric hypoxia postconditioning reduces brain damage and improves antioxidative defense in the model of birth asphyxia in 7-day-old rats. Neurochem Res 39(1):68–75CrossRefPubMedGoogle Scholar
  5. Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239(1):57–69CrossRefPubMedGoogle Scholar
  6. Kirino T, Sano K (1984) Selective vulnerability in the gerbil hippocampus following transient ischemia. Acta Neuropathol 62(3):201–208CrossRefPubMedGoogle Scholar
  7. Koh PO (2008) Melatonin prevents ischemic brain injury through activation of the mTOR/p70S6 kinase signaling pathway. Neurosci Lett 444(1):74–78CrossRefPubMedGoogle Scholar
  8. Kovacina KS, Park GY, Bae SS et al (2003) Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J Biol Chem 278(12):10189–10194CrossRefPubMedGoogle Scholar
  9. Lee CH, Park JH, Yoo KY et al (2011) Pre- and post-treatments with escitalopram protect against experimental ischemic neuronal damage via regulation of BDNF expression and oxidative stress. Exp Neurol 229(2):450–459CrossRefPubMedGoogle Scholar
  10. Lee CH, Park JH, Cho JH et al (2014) Changes and expressions of Redd1 in neurons and glial cells in the gerbil hippocampus proper following transient global cerebral ischemia. J Neurol Sci 344(1–2):43–50CrossRefPubMedGoogle Scholar
  11. Liu BN, Han BX, Liu F (2014) Neuroprotective effect of pAkt and HIF-1 alpha on ischemia rats. Asian Pac J Trop Med 7(3):221–225CrossRefPubMedGoogle Scholar
  12. Loskota WA, Lomax P, Verity MA (1974) A stereotaxic atlas of the Mongolian Gerbil Brain (Meriones unguiculatus). Ann Arbor Science Publishers Inc, MichiganGoogle Scholar
  13. Noshita N, Lewen A, Sugawara T et al (2001) Evidence of phosphorylation of Akt and neuronal survival after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 21(12):1442–1450CrossRefPubMedGoogle Scholar
  14. Park JH, Park OK, Cho JH et al (2014) Anti-inflammatory effect of tanshinone I in neuroprotection against cerebral ischemia-reperfusion injury in the gerbil hippocampus. Neurochem Res 39(7):1300–1312CrossRefPubMedGoogle Scholar
  15. Pastor MD, Garcia-Yebenes I, Fradejas N et al (2009) mTOR/S6 kinase pathway contributes to astrocyte survival during ischemia. J Biol Chem 284(33):22067–22078CrossRefPubMedGoogle Scholar
  16. Saito A, Narasimhan P, Hayashi T et al (2004) Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal cell death after stroke: relationships with nerve growth factor. J Neurosci 24(7):1584–1593CrossRefPubMedGoogle Scholar
  17. Saito A, Hayashi T, Okuno S et al (2006) Modulation of proline-rich akt substrate survival signaling pathways by oxidative stress in mouse brains after transient focal cerebral ischemia. Stroke 37(2):513–517CrossRefPubMedGoogle Scholar
  18. Sancak Y, Thoreen CC, Peterson TR et al (2007) PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 25(6):903–915CrossRefPubMedGoogle Scholar
  19. Schmued LC, Hopkins KJ (2000) Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874(2):123–130CrossRefPubMedGoogle Scholar
  20. Shi GD, OuYang YP, Shi JG et al (2011) PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway. Biochem Biophys Res Commun 404(4):941–945CrossRefPubMedGoogle Scholar
  21. Wang L, Harris TE, Roth RA et al (2007) PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem 282(27):20036–20044CrossRefPubMedGoogle Scholar
  22. Wen XR, Fu YY, Liu HZ et al (2015) Neuroprotection of sevoflurane against ischemia/reperfusion-induced brain injury through inhibiting JNK3/caspase-3 by enhancing Akt signaling pathway. Mol Neurobiol. doi: 10.1007/s12035-015-9111-8 Google Scholar
  23. Xiong X, Xie R, Zhang H et al (2014) PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways. Neurobiol Dis 66:43–52CrossRefPubMedPubMedCentralGoogle Scholar
  24. Yan BY, Pan CS, Mao XW et al (2014) Icariside II improves cerebral microcirculatory disturbance and alleviates hippocampal injury in gerbils after ischemia-reperfusion. Brain Res 1573:63–73CrossRefPubMedGoogle Scholar
  25. Yu F, Narasimhan P, Saito A et al (2008) Increased expression of a proline-rich Akt substrate (PRAS40) in human copper/zinc-superoxide dismutase transgenic rats protects motor neurons from death after spinal cord injury. J Cereb Blood Flow Metab 28(1):44–52CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Joon Ha Park
    • 1
  • Bich Na Shin
    • 2
  • Ji Hyeon Ahn
    • 1
  • Jeong-Hwi Cho
    • 1
  • In Hye Kim
    • 1
  • Dae Won Kim
    • 3
  • Moo-Ho Won
    • 1
  • Seongkweon Hong
    • 4
  • Jun Hwi Cho
    • 5
    Email author
  • Choong-Hyun Lee
    • 6
    Email author
  1. 1.Department of Neurobiology, School of MedicineKangwon National UniversityChuncheonSouth Korea
  2. 2.Department of Physiology, College of MedicineHallym UniversityChuncheonSouth Korea
  3. 3.Department of Biochemistry and Molecular Biology, College of Dentistry, and Research Institute of Oral SciencesKangnung-Wonju National UniversityGangneungSouth Korea
  4. 4.Department of Surgery, School of MedicineKangwon National UniversityChuncheonSouth Korea
  5. 5.Department of Emergency Medicine, College of Medicine, School of MedicineKangwon National UniversityChuncheonSouth Korea
  6. 6.Department of Pharmacy, College of PharmacyDankook UniversityCheonanSouth Korea

Personalised recommendations