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Cited by 518

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine

Open access
Heneka, Michael T., Nadrigny, Fabian, Regen, Tommy, Martinez-Hernandez, Ana, Dumitrescu-Ozimek, Lucia, Terwel, Dick, Jardanhazi-Kurutz, Daniel, Walter, Jochen, Kirchhoff, Frank, Hanisch, Uwe-Karsten, Kummer, Markus P.·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0909586107
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Abstract

Locus ceruleus (LC)-supplied norepinephrine (NE) suppresses neuroinflammation in the brain. To elucidate the effect of LC degeneration and subsequent NE deficiency on Alzheimer's disease pathology, we evaluated NE effects on microglial key functions. NE stimulation of mouse microglia suppressed Aβ-induced cytokine and chemokine production and increased microglial migration and phagocytosis of Aβ. Induced degeneration of the locus ceruleus increased expression of inflammatory mediators in APP-transgenic mice and resulted in elevated Aβ deposition. In vivo laser microscopy confirmed a reduced recruitment of microglia to Aβ plaque sites and impaired microglial Aβ phagocytosis in NE-depleted APP-transgenic mice. Supplying the mice the norepinephrine precursor L-threo-DOPS restored microglial functions in NE-depleted mice. This indicates that decrease of NE in locus ceruleus projection areas facilitates the inflammatory reaction of microglial cells in AD and impairs microglial migration and phagocytosis, thereby contributing to reduced Aβ clearance. Consequently, therapies targeting microglial phagocytosis should be tested under NE depletion.

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Metadata

Authors
Heneka, M. T., Nadrigny, F., Regen, T., Martinez-Hernandez, A., Dumitrescu-Ozimek, L., Terwel, D., Jardanhazi-Kurutz, D., Walter, J., Kirchhoff, F., Hanisch, U.-K., & Kummer, M. P.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2010-03-15
Volume
107
Issue
13
Pages
6058-6063
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0909586107
OpenAlex
W2168451388
Cited by
518
References
6
FWCI
15.65
Type
journal article
Language
en
Open access
green

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