Cited by 116Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer’s disease

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Kalinin, Sergey, Polak, Paul E., Lin, Shao Xia, Sakharkar, Amul J., Pandey, Subhash C., Feinstein, Douglas L.·2012·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2011.04.012PMC PMC3646366

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Abstract

Damage to noradrenergic neurons in the locus coeruleus (LC) is a hallmark of Alzheimer's disease (AD) and may contribute to disease progression. In 5xFAD transgenic mice, which accumulate amyloid burden at early ages, the LC undergoes stress as evidenced by increased astrocyte activation, neuronal hypertrophy, reduced levels of LC-enriched messenger RNAs (mRNAs), and increased inflammatory gene expression. Central nervous system (CNS) noradrenaline (NA) levels in 5-month-old male 5xFAD mice were increased using the NA precursor L-threo-3,4-dihydroxyphenylserine (L-DOPS). After 1 month, L-DOPS treatment improved learning in the Morris water maze test compared with vehicle-treated mice. L-DOPS increased CNS NA levels, and average latency times in the water maze test were inversely correlated to NA levels. L-DOPS reduced astrocyte activation and Thioflavin-S staining; increased mRNA levels of neprilysin and insulin degrading enzyme, and of several neurotrophins; and increased brain-derived neurotrophic factor protein levels. These data demonstrate the presence of LC stress in a robust mouse model of AD, and suggest that raising CNS NA levels could provide benefit in AD.

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Authors: Kalinin, S., Polak, P. E., Lin, S. X., Sakharkar, A. J., Pandey, S. C., & Feinstein, D. L.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Feinstein, Douglas L.
ORCID: Kalinin, Sergey
Polak, Paul E.
Sakharkar, Amul J.
Pandey, Subhash C.
Feinstein, Douglas L.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2012-08
Volume: 33
Issue: 8
Pages: 1651-1663
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2011.04.012
PMC: PMC3646366
OpenAlex: W1991513124
Cited by: 116
References: 59
Citations by year: 2026: 4 · 2025: 6 · 2024: 7 · 2023: 2 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 15 · 2016: 11 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 5
FWCI: 5.67
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Department of Veterans Affairs
American Alzheimer's Association
NIH (RO1-AA010005)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, norepinephrine, locus coeruleus, 5xFAD mice, amyloid, astrocyte activation, neuroinflammation, learning disabilities, brain-derived neurotrophic factor, neprilysin, insulin-degrading enzyme, neurotrophins, noradrenergic neurons
MeSH terms: Alzheimer Disease, Animals, Antiparkinson Agents, Locus Coeruleus, Male, Mice, Transgenic, Norepinephrine, Droxidopa, Treatment Outcome, Maze Learning, Mice, Adrenergic Neurons

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The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer’s disease

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