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 accessAbstract
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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Cites
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676
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Self-citationNEURONAL DEGENERATION IN LOCUS CERULEUS AND CORTICAL CORRELATES OF ALZHEIMER DISEASE
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BackgroundGGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide
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Self-citationIncreased activity of surviving locus ceruleus neurons in Alzheimer's disease
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Cited by
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
Self-citationNLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898
Self-citationRole of pro-inflammatory cytokines released from microglia in Alzheimer's disease.
(2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2015.03.49 · Cited by 1,288
Microglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902
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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
- Published
- 2010-03-15
- Volume
- 107
- Issue
- 13
- Pages
- 6058-6063
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2168451388
- Cited by
- 518
- References
- 6
- FWCI
- 15.65
- Type
- journal article
- Language
- en
- Open access
- green
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- 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. (2010). Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0909586107
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