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 [F] Diseases Research  / PubMed Research Articles  /
Beta estradiol and norepinephrine treatment of differentiated SH-SY5Y cells enhances tau phosphorylation at (Ser396) and (Ser262) via AMPK but not mTOR signaling pathway.




Molecular and cellular neurosciences Feb ; ()


Majd S1; Majd Z2; Koblar S3; Power J4;

Author Information
  • 1Neuronal Injury and Repair (NIR) Laboratory, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, Australia. Electronic address: shohreh.majd@flinders.edu.au.
  • 2Psychosomatische Tagesklinic, Stadtturm, Passau, Bavaria, Germany.
  • 3School of Medicine, The Queen Elizabeth Hospital (TQEH) campus, University of Adelaide, Australia.
  • 4Neuronal Injury and Repair (NIR) Laboratory, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, Australia.


Hyperphosphorylation of tau is one of the main hallmarks for Alzheimer's disease (AD) and many other tauopathies. Norepinephrine (NE), a stress-related hormone 17-β-estradiol (E2) and thought to influence tau phosphorylation (p-tau) and AD pathology. The controversy around the impact of NE and E2 requires further clarification. Moreover, the combination effect of physiological and psychological stress and estrogen alteration during menopause, which affect p-tau, has not been addressed. Exposure to E2 is believed to reduce NE release, however, the link between these two hormones and AD at cellular level was also remained unknown. Here, we examined whether NE and E2 treatment of differentiated SH-SY5Y cells affected tau phosphorylation. The involvement of adenosine monophosphate kinase protein kinase (AMPK) and target of Rapamycin (mTOR) as the possible mechanisms, underlying this effect was also investigated. Subsequent to SH-SY5Y differentiation to mature neurons, we treated the cells with NE, E2 and NE plus E2 in presence and absence of Compound C and Rapamycin. Cell viability was not affected by our treatment while our Western blot and immunofluorescent findings showed that exposure to NE and E2 separately, and in combination enhanced p-tau (Ser396) and (Ser262)/tau but not (Ser202/Thr205)/tau. Blocking AMPK by Compound C reduced p-tau (Ser396) and (Ser262), while GSK-3β and PP2A activities were remained unchanged. We also found that blocking mTOR by Rapamycin did not change increased p-tau (Ser396) and (Ser262) due to NE + E2 treatment. Collectively, our results suggested that tau hyperphosphorylation due to exposure to NE/E2 was mediated by AMPK, the main energy regulator of cells during stress with no significant involvement of mTOR, GSK-3β and PP2A.

Copyright © 2017. Published by Elsevier Inc.




Publication Type: Journal Article

This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.

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