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Author Notes:

Correspondence to: Keqiang Ye, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Whitehead 145, 615 Michael St., Atlanta, GA 30322, USA. Tel.: +1 404 712 2814; Fax: +1 404 712 2979; E-mail: kye@emory.edu

Correspondence to: David Weinshenker, Department of Human Genetics, Emory University School of Medicine, Whitehead 301, 615 Michael St., Atlanta, GA 30322, USA. Tel.: +1 404 727 3106; Fax: +1 404 727 3949; E-mail: dweinsh@emory.edu

Subjects:

Research Funding:

This work was funded by the National Institutes of Health (AG025688 to DW and KY, DC010204 to KY).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Alzheimer's disease
  • amyloid-beta
  • brain-derived neurotrophic factor
  • locus coeruleus
  • neuroprotection
  • norepinephrine
  • tropomyosin-related kinase B
  • ALZHEIMERS-DISEASE
  • LOCUS-CERULEUS
  • MOUSE MODEL
  • NEUROTROPHIC FACTOR
  • MEMORY DEFICITS
  • TRANSGENIC MOUSE
  • OXIDATIVE STRESS
  • BRAIN
  • NEURONS
  • BDNF

Norepinephrine Protects against Amyloid-beta Toxicity via TrkB

Tools:

Journal Title:

Journal of Alzheimer's Disease

Volume:

Volume 44, Number 1

Publisher:

, Pages 251-260

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The locus coeruleus (LC), the brainstem noradrenergic nucleus that is the sole source of norepinephrine (NE) in the forebrain, is one of the first structures affected in Alzheimer's disease (AD). Experimental ablation of the LC exacerbates, while increasing NE abates, AD-like neuropathology and cognitive deficits in animal models of the disease. Some neuroprotective effects of NE appear to be mediated by tropomyosin-related kinase B (TrkB), the canonical receptor for brain-derived neurotrophic factor (BDNF). Here, we report that NE dose-dependently protected primary cortical and LC neurons from amyloid-β (Aβ) toxicity. The neuroprotective effects of NE were fully prevented by the Trk receptor antagonist K252a but only partially attenuated by adrenergic receptor antagonists and not mimicked by adrenergic agonists. Activation of TrkB by NE in cortical and LC neurons was confirmed by immunoblot and immunocytochemistry for phospho-TrkB. These results indicate that NE can activate TrkB and protect against Aβ toxicity, at least in part, via adrenergic receptor-independent mechanisms, and have implications for the consequences of LC degeneration in AD and potential therapies for the disease.

Copyright information:

© 2015-IOS Press and the authors. All rights reserved.

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