369
Views
7
CrossRef citations to date
0
Altmetric
Reviews

The role of mTOR signalling pathway in hypoxia-induced cognitive impairment

, , , , , & show all
Pages 482-488 | Received 18 Dec 2019, Accepted 11 Mar 2020, Published online: 02 Apr 2020

References

  • Mukandala G, Tynan R, Lanigan S, et al. The effects of hypoxia and inflammation on synaptic signaling in the CNS. Brain Sci. 2016;6(1):6. pii:
  • Maiti P, Singh SB, Muthuraju S, et al. Hypobaric hypoxia damages the hippocampal pyramidal neurons in the rat brain. Brain Res. 2007;1175:1–9.
  • Barhwal K, Hota SK, Baitharu I, et al. Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment: complementary roles of L-type calcium channel and NMDA receptors. Neurobiol Dis.. 2009;34(2):230–244.
  • Hota SK, Barhwal K, Baitharu I, et al. Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment. Neurobiol Dis.. 2009;34(1):23–39.
  • Barhwal K, Singh SB, Hota SK, et al. Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats. Eur J Pharmacol.. 2007;570(1-3):97–107.
  • Jayalakshmi K, Singh S, Kalpana B, et al. N-acetyl cysteine supplementation prevents impairment of spatial working memory functions in rats following exposure to hypobaric hypoxia. Physiol Behav.. 2007;92(4):643–650.
  • Baitharu I, Deep SN, Jain V, et al. Inhibition of glucocorticoid receptors ameliorates hypobaric hypoxia induced memory impairment in rat. Behav Brain Res.. 2013;240:76–86.
  • Qaid E, Zakaria R, Sulaiman SF, et al. Insight into potential mechanisms of hypobaric hypoxia–induced learning and memory deficit – Lessons from rat studies. Hum Exp Toxicol. 2017;36(12):1315–1325.
  • Kumar R, Jain V, Kushwah N, et al. Role of DNA methylation in hypobaric hypoxia-induced neurodegeneration and spatial memory impairment. Ann Neurosci. 2018;25(4):191–200.
  • Alam S, Ray K, Jain V, et al. Reduced expression of Kalirin-7 contributes to working memory deficit during chronic hypobaric hypoxia exposure. Behav Brain Res.. 2019;366:135–141.
  • Harman MF, Martín MG. Epigenetic mechanisms related to cognitive decline during aging. J Neurosci Res.. 2020;98(2):234–246.
  • Jaworski J, Sheng M. The growing role of mTOR in neuronal development and plasticity. Mol Neurobiol.. 2006;34(3):205–219.
  • Garelick MG, Kennedy BK. TOR on the brain. Exp Gerontol.. 2011;46(2-3):155–163.
  • Koh PO. Nicotinamide attenuates the ischemic brain injury-induced decrease of Akt activation and Bad phosphorylation. Neurosci Lett.. 2011;498(2):105–109.
  • Shang YC, Chong ZZ, Wang S, et al. Erythropoietin and Wnt1 govern pathways of mTOR, Apaf-1, and XIAP in inflammatory microglia. Curr Neurovasc Res. 2011;8(4):270–285.
  • Zeng KW, Wang XM, Ko H, et al. Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid β-protein via the PI3K/Akt/Bad/Bcl(XL)- regulated mitochondrial apoptotic pathway. Eur J Pharmacol.. 2011;672(1-3):45–55.
  • Lipton JO, Sahin M. The neurology of mTOR. Neuron. 2014;84(2):275–291.
  • McMorris T, Hale BJ, Barwood M, et al. Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis. Neurosci Biobehav Rev. 2017;74(Pt A):225–232.
  • Yang L, Zhang Y, Yan Z, et al. The role of mTOR signaling pathway on cognitive functions in cerebral ischemia-reperfusion. Exp Ther Med. 2017;14(4):2839–2844.
  • Tischmeyer W, Schicknick H, Kraus M, et al. Rapamycin-sensitive signalling in long-term consolidation of auditory cortex-dependent memory. Eur J Neurosci.. 2003;18(4):942–950.
  • Parsons RG, Gafford GM, Helmstetter FJ. Translational control via the mammalian target of rapamycin pathway is critical for the formation and stability of long-term fear memory in amygdala neurons. J Neurosci.. 2006;26(50):12977–12983.
  • Bekinschtein P, Katche C, Slipczuk LN, et al. mTOR signaling in the hippocampus is necessary for memory formation. Neurobiol Learn Mem. 2007;87(2):303–307.
  • Blundell J, Kouser M, Powell CM. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem. 2008;90(1):28–35.
  • Belelovsky K, Kaphzan H, Elkobi A, et al. Biphasic activation of the mTOR pathway in the gustatory cortex is correlated with and necessary for taste learning. J Neurosci.. 2009;29(23):7424–7431.
  • Glover EM, Ressler KJ, Davis M. Differing effects of systemically administered rapamycin on consolidation and reconsolidation of context vs. cued fear memories. Learn Mem.. 2010;17(11):577–581.
  • Gafford GM, Parsons RG, Helmstetter FJ. Consolidation and reconsolidation of contextual fear memory requires mammalian target of rapamycin-dependent translation in the dorsal hippocampus. Neuroscience. 2011;182:98–104.
  • Deli A, Schipany K, Rosner M, et al. Blocking mTORC1 activity by rapamycin leads to impairment of spatial memory retrieval but not acquisition in C57BL/6J mice. Behav Brain Res. 2012;229(2):320–324.
  • Halloran J, Hussong SA, Burbank R, et al. Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience. 2012;223:102–113.
  • Jobim PF, Pedroso TR, Christoff RR, et al. Inhibition of mTOR by rapamycin in the amygdala or hippocampus impairs formation and reconsolidation of inhibitory avoidance memory. Neurobiol Learn Mem. 2012;97(1):105–112.
  • Huang W, Zhu PJ, Zhang S, et al. mTORC2 controls actin polymerization required for consolidation of long-term memory. Nat Neurosci.. 2013;16(4):441–448.
  • Wen ZW, Liang DS, Cai XH, et al. The role of AMPK/mTOR signal pathway in brain injury following chronic intermittent hypoxia in growing rats. Eur Rev Med Pharmacol Sci. 2018;22(4):1071–1077.
  • Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol.. 2005;17(6):596–603.
  • Weber JD, Gutmann DH. Deconvoluting mTOR biology. Cell Cycle. 2012;11(2):236–248.
  • Chen H, Xiong T, Qu Y, Zhao F, et al. mTOR activates hypoxia-inducible factor-1α and inhibits neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia. Neurosci Lett.. 2012;507(2):118–123.
  • Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274–293.
  • Zhou H, Huang S. Role of mTOR signaling in tumor cell motility, invasion and metastasis. Curr Protein Pept Sci.. 2011;12(1):30–42.
  • Giovannini MG, Lana D. 2016. mTOR Involvement in the mechanisms of memory In: K. Maiese editor. Molecules to medicine with mTOR: translating critical pathways into novel therapeutic strategies. Newark, NJ, USA: Academic Press. pp. 169–184.
  • Puighermanal E, Busquets-Garcia A, Maldonado R, et al. Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids. Philos Trans R Soc Lond, B, Biol Sci.. 2012;367(1607):3254–3263.
  • Troca-Marín JA, Alves-Sampaio A, Montesinos ML. Deregulated mTORmediated translation in intellectual disability. Prog Neurobiol. 2012;96(2):268–282.
  • Squire LR, Davis HP. The pharmacology of memory: A neurobiological perspective. Annu Rev Pharmacol Toxicol.. 1981;21:323–356.
  • Takei N, Nawa H. mTOR signaling and its roles in normal and abnormal brain development. Front Mol Neurosci. 2014;7:28
  • Pereyra M, Katche CE, Landeta AB, et al. mTORC1 controls long-term memory retrieval. Sci Rep. 2018;8(1):8759.
  • Lana D, Di Russo J, Mello T, et al. Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory. Neurobiol Learn Mem. 2017;137:15–26.
  • Wang N, He J, Pan C, et al. Resveratrol activates autophagy via the AKT/mTOR signaling pathway to improve cognitive dysfunction in rats with chronic cerebral hypoperfusion. Front Neurosci. 2019;13:859
  • Li W, Petrimpol M, Molle KD, et al. Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2. Circ Res.. 2007;100(1):79–87.
  • Bernardi R, Guernah I, Jin D, et al. PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR. Nature. 2006;442(7104):779–785.
  • Gerasimovskaya EV, Tucker DA, Stenmark KR. Activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin is necessary for hypoxia-induced pulmonary artery adventitial fibroblast proliferation. J Appl Physiol.. 2005;98(2):722–731.
  • Humar R, Kiefer FN, Berns H, et al. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling. FASEB J. 2002;16(8):771–780.
  • Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol.. 2002;22(20):7004–7014.
  • Brugarolas J, Lei K, Hurley RL, et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 2004;18(23):2893–2904. Jr
  • Connolly E, Braunstein S, Formenti S, et al. Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells. Mol Cell Biol.. 2006;26(10):3955–3965.
  • Lee HJ, Koh SH, Song KM, et al. The Akt/mTOR/p70S6K Pathway Is Involved in the Neuroprotective Effect of Erythropoietin on Hypoxic/Ischemic Brain Injury in a Neonatal Rat Model. Neonatology. 2016;110(2):93–100.
  • Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol.. 1992;12(12):5447–5454.
  • Zhang Z, Yao L, Yang J, et al. PI3K/Akt and HIF–1 signaling pathway in hypoxia–ischemia (Review) ). Mol Med Rep. 2018;18(4):3547–3554.
  • Sharp FR, Bernaudin M. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci.. 2004;5(6):437–448.
  • Yuan G, Nanduri J, Khan S, et al. Induction of HIF-1a expression by intermittent hypoxia: Involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol.. 2008;217(3):674–685.
  • Land SC, Tee AR. Hypoxia-inducible factor 1a is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem.. 2007;282(28):20534–20543.
  • DeYoung MP, Horak P, Sofer A, et al. Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling. Genes Dev. 2008;22(2):239–251.
  • Ellisen LW. Growth control under stress: mTOR regulation through the REDD1-TSC pathway. Cell Cycle. 2005;4(11):1500–1502.
  • Baranova O, Miranda LF, Pichiule P, et al. Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci.. 2007;27(23):6320–6332.
  • Helton R, Cui J, Scheel JR, et al. Brain-specific knock-out of hypoxia-inducible factor-1alpha reduces rather than increases hypoxic-ischemic damage. J Neurosci.. 2005;25(16):4099–4107.
  • Aramburu J, Ortells MC, Tejedor S, et al. Transcriptional regulation of the stress response by mTOR. Sci Signal. 2014;7(332):re2.
  • Koong AC, Chen EY, Giaccia AJ. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res. 1994;54(6):1425–1430.
  • Yeo E. Hypoxia and aging. Exp Mol Med. 2019;51(6):1–15.
  • Bowser JL, Lee JW, Yuan X, et al. The hypoxia-adenosine link during inflammation. J Appl Physiol.. 2017;123(5):1303–1320.
  • Yuan X, Lee JW, Bowser JL, et al. Targeting hypoxia signaling for perioperative organ injury. Anesth Analg.. 2018;126(1):308–321.
  • Kiers D, Wielockx B, Peters E, van Eijk LT, et al. Short-term hypoxia dampens inflammation in vivo via enhanced adenosine release and adenosine 2B receptor stimulation. EBioMedicine. 2018;33:144–156.
  • Bowser JL, Phan LH, Eltzschig HK. The hypoxia-adenosine link during intestinal inflammation. J Immunol.. 2018;200(3):897–907.
  • Eltzschig HK, Ko D, Eckle T, et al. Central role of Sp1-regulated CD39 in hypoxia/ischemia protection. Blood. 2009;113(1):224–232.
  • Eltzschig HK, Abdulla P, Hoffman E, Hamilton KE, et al. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J Exp Med.. 2005;202(11):1493–1505.
  • Lee CH, Inoki K, Karbowniczek M, et al. Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53. EMBO J. 2007;26(23):4812–4823.
  • Choo AY, Kim SG, Vander Heiden MG, et al. Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol Cell.. 2010;38(4):487–499.
  • Aravamudan B, Thompson M, Pabelick C, et al. Brain derived neurotrophic factor induces proliferation of human airway smooth muscle cells. J Cell Mol Med.. 2012;16(4):812–823.
  • Helan M, Aravamudan B, Hartman WR, Thompson MA, et al. BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia. J Mol Cell Cardiol.. 2014;68:89–97.
  • Becke A, Müller P, Dordevic M, et al. Daily intermittent normobaric hypoxia over 2 weeks reduces BDNF plasma levels in young adults - A randomized controlled feasibility study. Front Physiol. 2018;9:1337
  • Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci.. 2001;24:677–736.
  • Leschik J, Eckenstaler R, Nieweg K, et al. Embryonic stem cells stably expressing BDNF-GFP exhibit a BDNF-release-dependent enhancement of neuronal differentiation. J Cell Sci.. 2013;126(Pt 21):5062–5073.
  • Park H, Poo MM. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci.. 2013;14(1):7–23.
  • Edelmann E, Leßmann V, Brigadski T. Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity. Neuropharmacology. 2014;76(Pt C):610–627.
  • Calabrese F, Rossetti AC, Racagni G, et al. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front Cell Neurosci. 2014;8:430
  • Vermehren-Schmaedick A, Jenkins VK, Knopp SJ, et al. Acute intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of methyl-CpG binding protein 2 null mice. Neuroscience. 2012;206:1–6.
  • Enette L, Vogel T, Fanon JL, et al. Effect of interval and continuous aerobic training on basal serum and plasma brain-derived neurotrophic factor values in seniors: a systematic review of intervention studies. Rejuvenation Res. 2017;20(6):473–483.
  • Wiener CM, Booth G, Semenza GL. In vivo expression of mRNAs encoding hypoxia-inducible factor 1. Biochem Biophys Res Commun.. 1996;225(2):485–488.
  • Scott AL, Zhang M, Nurse CA. Enhanced BDNF signalling following chronic hypoxia potentiates catecholamine release from cultured rat adrenal chromaffin cells. J Physiol..). 2015;593(15):3281–3299.
  • Takei N, Inamura N, Kawamura M, et al. Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. J Neurosci.. 2004;24(44):9760–9769.
  • Slipczuk L, Bekinschtein P, Katche C, et al. BDNF activates mTOR to regulate GluR1 expression required for memory formation. PLoS ONE. 2009;4(6):e6007.
  • Inamura N, Nawa H, Takei N. Enhancement of translation elongation in neurons by brain-derived neurotrophic factor: implications for mammalian target of rapamycin signaling. J Neurochem.. 2005;95(5):1438–1445.
  • Schratt GM, Nigh EA, Chen WG, et al. BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development. J Neurosci.. 2004;24(33):7366–7377.
  • Thoenen H. Neurotrophins and neuronal plasticity. Science. 1995;270(5236):593–598.
  • Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci.. 2001;2(1):24–32.
  • Santos AR, Comprido D, Duarte CB. Regulation of local translation at the synapse by BDNF. Prog Neurobiol.. 2010;92(4):505–516.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.