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Article

Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation

  • Authors:
    • Wenzhen Shen
    • Keliang Lu
    • Jiawan Wang
    • Anshi Wu
    • Yun Yue
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China, Department of Anesthesiology, Weifang Medical University, Weifang, Shandong 261031, P.R. China
  • Pages: 3925-3934
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    Published online on: September 1, 2016
       https://doi.org/10.3892/mmr.2016.5700
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Abstract

Postoperative cognitive dysfunction (POCD) is a serious complication following surgery, however, the mechanism of POCD remains to be elucidated. Previous evidence has revealed that POCD may be associated with the pathogenesis of neurodegenerative processes. The mammalian target of rapamycin (mTOR) signaling pathway has been reported to be crucial in the pathophysiology of neurodegenerative diseases. However, the implications of mTOR in POCD remains to be fully elucidated. In the present study, western blotting and enzyme‑linked immunosorbent assay were used to determine the expression of mTOR and any associated downstream targets; contextual fear conditioning was used to estimate the learning and memory ability of mice. Using an animal model of orthopedic surgery, it was found that surgical injury impaired hippocampal‑dependent memory and enhanced the levels of phosphorylated mTOR at Serine‑2448, phosphorylated 70‑kDa ribosomal protein S6 kinase (p70S6K) at Threonine‑389 with accumulation of β‑amyloid (Aβ) and hyperphosphorylated tau at Serine-396, compared with the control group. Pretreatment with rapamycin, an mTOR inhibitor, restored the abnormal mTOR/p70S6K signaling induced by surgery, attenuated the accumulation of Aβ and reduced the phosphorylation of tau protein. Rapamycin also reversed the surgery‑induced cognitive dysfunction. The results of the present study suggested that the surgical stimulus activated mTOR/p70S6K signaling excessively, and that the inhibition of mTOR signaling with rapamycin may prevent postoperative cognitive deficits, partly through attenuating the accumulation of Aβ and hyperphosphorylation of tau protein.
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View References

1 

Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, et al: Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators International Study of Post-Operative Cognitive Dysfunction. Lancet. 351:857–861. 1998. View Article : Google Scholar : PubMed/NCBI

2 

Rubens FD, Boodhwani M and Nathan H: Interpreting studies of cognitive function following cardiac surgery: A guide for surgical teams. Perfusion. 22:185–192. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Newman S, Stygall J, Hirani S, Shaefi S and Maze M: Postoperative cognitive dysfunction after noncardiac surgery: A systematic review. Anesthesiology. 106:572–590. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Vacas S, Degos V, Feng X and Maze M: The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 106:161–78. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Krenk L, Rasmussen LS and Kehlet H: New insights into the pathophysiology of postoperative cognitive dysfunction. Acta Anaesthesiol Scand. 54:951–956. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Wang C, Yu JT, Miao D, Wu ZC, Tan MS and Tan L: Targeting the mTOR signaling network for Alzheimer's disease therapy. Mol Neurobiol. 49:120–135. 2014. View Article : Google Scholar

7 

Hoeffer CA and Klann E: mTOR signaling: At the crossroads of plasticity, memory and disease. Trends Neurosci. 33:67–75. 2010. View Article : Google Scholar

8 

Banko JL, Merhav M, Stern E, Sonenberg N, Rosenblum K and Klann E: Behavioral alterations in mice lacking the translation repressor 4E-BP2. Neurobiol Learn Mem. 87:248–256. 2007. View Article : Google Scholar

9 

Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski DJ, Ramesh V and Silva AJ: Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis. Nat Med. 14:843–848. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Garelick MG and Kennedy BK: TOR on the brain. Exp Gerontol. 46:155–163. 2011. View Article : Google Scholar

11 

Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J and Pedraza-Chaverri J: The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 26:2694–2701. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Li X, Alafuzoff I, Soininen H, Winblad B and Pei JJ: Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain. FEBS J. 272:4211–4220. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Caccamo A, Majumder S, Richardson A, Strong R and Oddo S: Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: Effects on cognitive impairments. J Biol Chem. 285:13107–13120. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, Richardson A, Strong R and Galvan V: Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One. 5:e99792010. View Article : Google Scholar : PubMed/NCBI

15 

Cao XZ, Ma H, Wang JK, Liu F, Wu BY, Tian AY, Wang LL and Tan WF: Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuropsychopharmacol Biol Psychiatry. 34:1426–1432. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Laplante M and Sabatini DM: mTOR signaling. Cold Spring Harb Perspect Biol. 4:22012. View Article : Google Scholar

17 

Lee DF, Kuo HP, Chen CT, Hsu JM, Chou CK, Wei Y, Sun HL, Li LY, Ping B, Huang WC, et al: IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell. 130:440–455. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Degos V, Vacas S, Han Z, van Rooijen N, Gressens P, Su H, Young WL and Maze M: Depletion of bone marrow-derived macrophages perturbs the innate immune response to surgery and reduces postoperative memory dysfunction. Anesthesiology. 118:527–536. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Vizcaychipi MP, Xu L, Barreto GE, Ma D, Maze M and Giffard RG: Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice. Anesthesiology. 114:891–900. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Vacas S, Degos V, Tracey KJ and Maze M: High-mobility group box 1 protein initiates postoperative cognitive decline by engaging bone marrow-derived macrophages. Anesthesiology. 120:1160–1167. 2014. View Article : Google Scholar :

21 

Erlich S, Alexandrovich A, Shohami E and Pinkas-Kramarski R: Rapamycin is a neuroprotective treatment for traumatic brain injury. Neurobiol Dis. 26:86–93. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Tang P, Hou H and Zhang L, Lan X, Mao Z, Liu D, He C, Du H and Zhang L: Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats. Mol Neurobiol. 49:276–287. 2014. View Article : Google Scholar

23 

Broadbent NJ, Squire LR and Clark RE: Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci USA. 101:14515–14520. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Maren S, Phan KL and Liberzon I: The contextual brain: Implications for fear conditioning, extinction and psychopathology. Nat Rev Neurosci. 14:417–428. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS and Maze M: Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 68:360–368. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, Jonsson Fagerlund M, Charo IF, Akassoglou K and Maze M: Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 70:986–995. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Hu N, Guo D, Wang H, Xie K, Wang C, Li Y, Wang C, Wang C, Yu Y and Wang G: Involvement of the blood-brain barrier opening in cognitive decline in aged rats following orthopedic surgery and high concentration of sevoflurane inhalation. Brain Res. 1551:13–24. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Majumder S, Caccamo A, Medina DX, Benavides AD, Javors MA, Kraig E, Strong R, Richardson A and Oddo S: Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling. Aging Cell. 11:326–335. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Caccamo A, Magri A, Medina DX, Wisely EV, López-Aranda MF, Silva AJ and Oddo S: mTOR regulates tau phosphorylation and degradation: Implications for Alzheimer's disease and other tauopathies. Aging Cell. 12:370–380. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Wang S, Zhou SL, Min FY, Ma JJ, Shi XJ, Bereczki E and Wu J: mTOR-mediated hyperphosphorylation of tau in the hippocampus is involved in cognitive deficits in streptozotocin-induced diabetic mice. Metab Brain Dis. 29:729–736. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Hoeffer CA, Tang W, Wong H, Santillan A, Patterson RJ, Martinez LA, Tejada-Simon MV, Paylor R, Hamilton SL and Klann E: Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron. 60:832–845. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Dash PK, Orsi SA and Moore AN: Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-Mammalian target of rapamycin pathway. J Neurosci. 26:8048–8056. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Schicknick H, Schott BH, Budinger E, Smalla KH, Riedel A, Seidenbecher CI, Scheich H, Gundelfinger ED and Tischmeyer W: Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR. Cereb Cortex. 18:2646–2658. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Puighermanal E, Marsicano G, Busquets-Garcia A, Lutz B, Maldonado R and Ozaita A: Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling. Nat Neurosci. 12:1152–1158. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Halloran J, Hussong SA, Burbank R, Podlutskaya N, Fischer KE, Sloane LB, Austad SN, Strong R, Richardson A, Hart MJ and Galvan V: Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience. 223:102–113. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Braak H and Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82:239–259. 1991. View Article : Google Scholar : PubMed/NCBI

37 

Blasko I, Kemmler G, Jungwirth S, Wichart I, Krampla W, Weissgram S, Jellinger K, Tragl KH and Fischer P: Plasma amyloid beta-42 independently predicts both late-onset depression and Alzheimer disease. Am J Geriatr Psychiatry. 18:973–982. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Wan Y, Xu J, Meng F, Bao Y, Ge Y, Lobo N, Vizcaychipi MP, Zhang D, Gentleman SM, Maze M and Ma D: Cognitive decline following major surgery is associated with gliosis, β-amyloid accumulation and tau phosphorylation in old mice. Crit Care Med. 38:2190–2198. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Reinsfelt B, Westerlind A, Blennow K, Zetterberg H and Ricksten SE: Open-heart surgery increases cerebrospinal fluid levels of Alzheimer-associated amyloid β. Acta Anaesthesiol Scand. 57:82–88. 2013. View Article : Google Scholar

40 

Ma YQ, Wu DK and Liu JK: mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease. Mol Med Rep. 7:623–627. 2013.

41 

Tang Z, Bereczki E, Zhang H, Wang S, Li C, Ji X, Branca RM, Lehtiö J, Guan Z, Filipcik P, et al: Mammalian target of rapamycin (mTor) mediates tau protein dyshomeostasis: Implication for Alzheimer disease. J Biol Chem. 288:15556–15570. 2013. View Article : Google Scholar : PubMed/NCBI

42 

Lyman M, Lloyd DG, Ji X, Vizcaychipi MP and Ma D: Neuro-inflammation: The role and consequences. Neurosci Res. 79:1–12. 2014. View Article : Google Scholar

43 

Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M and Maze M: Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA. 107:20518–20522. 2010. View Article : Google Scholar : PubMed/NCBI

44 

Zhu XC, Yu JT, Jiang T and Tan L: Autophagy modulation for Alzheimer's disease therapy. Mol Neurobiol. 48:702–714. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Shen W, Lu K, Wang J, Wu A and Yue Y: Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation. Mol Med Rep 14: 3925-3934, 2016.
APA
Shen, W., Lu, K., Wang, J., Wu, A., & Yue, Y. (2016). Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation. Molecular Medicine Reports, 14, 3925-3934. https://doi.org/10.3892/mmr.2016.5700
MLA
Shen, W., Lu, K., Wang, J., Wu, A., Yue, Y."Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation". Molecular Medicine Reports 14.4 (2016): 3925-3934.
Chicago
Shen, W., Lu, K., Wang, J., Wu, A., Yue, Y."Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation". Molecular Medicine Reports 14, no. 4 (2016): 3925-3934. https://doi.org/10.3892/mmr.2016.5700
Copy and paste a formatted citation
x
Spandidos Publications style
Shen W, Lu K, Wang J, Wu A and Yue Y: Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation. Mol Med Rep 14: 3925-3934, 2016.
APA
Shen, W., Lu, K., Wang, J., Wu, A., & Yue, Y. (2016). Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation. Molecular Medicine Reports, 14, 3925-3934. https://doi.org/10.3892/mmr.2016.5700
MLA
Shen, W., Lu, K., Wang, J., Wu, A., Yue, Y."Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation". Molecular Medicine Reports 14.4 (2016): 3925-3934.
Chicago
Shen, W., Lu, K., Wang, J., Wu, A., Yue, Y."Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through β-amyloid accumulation and tau phosphorylation". Molecular Medicine Reports 14, no. 4 (2016): 3925-3934. https://doi.org/10.3892/mmr.2016.5700
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