PMID- 25208620
OWN - NLM
STAT- MEDLINE
DCOM- 20150910
LR  - 20211021
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 44
IP  - 1
DP  - 2015
TI  - Norepinephrine Protects against Amyloid-beta Toxicity via TrkB.
PG  - 251-60
LID - 10.3233/JAD-141062 [doi]
AB  - 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-beta (Abeta) 
      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 Abeta 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.
FAU - Liu, Xia
AU  - Liu X
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA, USA.
FAU - Ye, Keqiang
AU  - Ye K
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, GA, USA.
FAU - Weinshenker, David
AU  - Weinshenker D
AD  - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 
      USA.
LA  - eng
GR  - P50 AG025688/AG/NIA NIH HHS/United States
GR  - R01 DC010204/DC/NIDCD NIH HHS/United States
GR  - AG025688/AG/NIA NIH HHS/United States
GR  - DC010204/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Adrenergic Agents)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (MAP2 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.22.- (Caspases)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic Agents/pharmacology
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/drug effects
MH  - Brain/cytology
MH  - Carbazoles/pharmacology
MH  - Caspases/metabolism
MH  - Cell Count
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Indole Alkaloids/pharmacology
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Norepinephrine/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Receptor, trkB/*metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
PMC - PMC4714587
MID - NIHMS749480
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - amyloid-beta
OT  - brain-derived neurotrophic factor
OT  - locus coeruleus
OT  - neuroprotection
OT  - norepinephrine
OT  - tropomyosin-related kinase B
COIS- The authors declare no conflicts of interest.
EDAT- 2014/09/12 06:00
MHDA- 2015/09/12 06:00
PMCR- 2016/01/15
CRDT- 2014/09/12 06:00
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2015/09/12 06:00 [medline]
PHST- 2016/01/15 00:00 [pmc-release]
AID - A63M352142K0436U [pii]
AID - 10.3233/JAD-141062 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2015;44(1):251-60. doi: 10.3233/JAD-141062.