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The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer’s disease
Open accessAbstract
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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“a reduced plaque burden has been shown to be accompanied by a reduced glial activation [6], [60].”
From Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease (2014) · cites this paper as [60]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 3×
“In these studies we used 5xFAD mice (Oakley et al., 2006), which harbor 3 mutations in the amyloid precursor protein (APP) gene and 2 in the presenilin-1 (PS1) gene; they accumulate soluble Aβ1–42 and develop plaques by 4 to 5 weeks age, and show frank neuronal damage including intraneuronal accumulation of Aβ1–42 and…”
BackgroundMethodThe locus coeruleus and noradrenergic modulation of cognition
Sara, S. J. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2573 · Cited by 1,848
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81827-9 · Cited by 1,782 · cited 1×
“Our findings that L-DOPS also reduced amyloid burden and inflammation in the hippocampus is consistent with the fact that learning in the Morris water maze test is considered to be dependent on hippocampal function (Tsien et al., 1996).”
ResultTrkB signalling pathways in LTP and learning
Minichiello, L. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2738 · Cited by 1,055
Zarow, C., Lyness, S. A., Mortimer, J. A., & Chui, H. C. (2003) · Archives of Neurology · doi:10.1001/archneur.60.3.337 · Cited by 1,003
Inflammatory processes in Alzheimer's disease
Heneka, M. T., & O'Banion, M. K. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.017 · Cited by 782
Peng, S., Wuu, J., Mufson, E. J., & Fahnestock, M. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03135.x · Cited by 691
Heneka, M. T., Nadrigny, F., Regen, T., Martinez-Hernandez, A., Dumitrescu‐Ozimek, L., Terwel, D., Jardanhazi‐Kurutz, D., Walter, J., Kirchhoff, F., Hanisch, U., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909586107 · Cited by 532
Disease‐specific patterns of locus coeruleus cell loss
German, D. C., Manaye, K. F., White, C. L., Woodward, D. J., McIntire, D. D., Smith, W. K., Kalaria, R. N., & Mann, D. M. A. (1992) · Annals of Neurology · doi:10.1002/ana.410320510 · Cited by 512
Samuels, E., & Szabadi, E. (2008) · Current Neuropharmacology · doi:10.2174/157015908785777193 · Cited by 454
Changes in the Brain Catecholamines in Patients with Dementia of Alzheimer Type
Adolfsson, R., Gottfries, C. G., Roos, B. E., & Winblad, B. G. (1979) · The British Journal of Psychiatry · doi:10.1192/bjp.135.3.216 · Cited by 449
Noradrenergic mechanisms in neurodegenerative diseases: a theory
Marien, M. R., Colpaert, F. C., & Rosenquist, A. C. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.02.002 · Cited by 425
Heneka, M. T., Ramanathan, M., Jacobs, A. H., Dumitrescu-Ozimek, L., Bilkei-Gorzo, A., Debeir, T., Sastre, M., Galldiks, N., Zimmer, A., Hoehn, M., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4236-05.2006 · Cited by 305
Temporal memory deficits in Alzheimer’s mouse models: Rescue by genetic deletion of BACE1
Ohno, M., Chang, L., Tseng, W., Oakley, H., Citron, M., Klein, W. L., Vassar, R., & Disterhoft, J. F. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04551.x · Cited by 298
Heneka, M. T., Galea, E., Gavriluyk, V., Dumitrescu‐Ozimek, L., Daeschner, J., O’Banion, M. K., Weinberg, G. L., Klockgether, T., & Feinstein, D. L. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02434.2002 · Cited by 255
Szot, P., White, S. S., Greenup, J. L., Leverenz, J. B., Peskind, E. R., & Raskind, M. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4265-05.2006 · Cited by 249
Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo
Arenas, E., & Persson, H. (1994) · Nature · doi:10.1038/367368a0 · Cited by 209
Wang, L. Y., Shofer, J. B., Rohde, K., Hart, K. L., Hoff, D. J., McFall, Y. H., Raskind, M. A., & Peskind, E. R. (2009) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181ab8c61 · Cited by 209
Liu, Y., Yoo, M.-J., Savonenko, A., Stirling, W., Price, D. L., Borchelt, D. R., Mamounas, L., Lyons, W. E., Blue, M. E., & Lee, M. K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4218-08.2008 · Cited by 206
Kalinin, S., Gavrilyuk, V., Polak, P. E., Vasser, R., Zhao, J. J., Heneka, M. T., & Feinstein, D. L. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.003 · Cited by 202
Self-citationFunctional Consequences of Locus Coeruleus Degeneration in Alzheimers Disease
Weinshenker, D. (2008) · Current Alzheimer Research · doi:10.2174/156720508784533286 · Cited by 180
Monoamine neurons in aging and Alzheimer's disease
Palmer, A. M., & DeKosky, S. T. (1993) · Journal of Neural Transmission · doi:10.1007/bf01245229 · Cited by 178
Interactions between APP secretases and inflammatory mediators
Sastre, M., Walter, J., & Gentleman, S. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-25 · Cited by 178
Functional Evidence that BDNF Is an Anterograde Neuronal Trophic Factor in the CNS
Fawcett, J. P., Bamji, S. X., Causing, C. G., Aloyz, R. S., Ase, A. R., Reader, T. A., McLean, J. H., & Miller, F. D. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02808.1998 · Cited by 174
NEURONAL DEGENERATION IN LOCUS CERULEUS AND CORTICAL CORRELATES OF ALZHEIMER DISEASE
Bondareff, W., Mountjoy, C. Q., Roth, M., Rossor, M. N., Iversen, L. L., Reynolds, G. P., & Hauser, D. L. (1987) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-198701040-00005 · Cited by 166 · cited 2×
“, 1992; Mann, 1983; Palmer and DeKosky, 1993; Weinshenker, 2008), and are correlated with plaque and tangle numbers (Bondareff et al., 1987) and duration of illness (Zarow et al.”
BackgroundRestoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome
Salehi, A., Faizi, M., Colas, D., Valletta, J. S., Laguna, J., Takimoto‐Kimura, R., Kleschevnikov, A. M., Wagner, S. L., Aisen, P. S. S., Shamloo, M., et al. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000258 · Cited by 161
Noradrenaline activation of neurotrophic pathways protects against neuronal amyloid toxicity
Counts, S., & Mufson, E. J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06622.x · Cited by 160
Neurotrophic factor therapy for Parkinson’s disease
Rangasamy, S. B., Soderstrom, K. E., Bakay, R. A. E., & Kordower, J. H. (2010) · Progress in brain research · doi:10.1016/s0079-6123(10)84013-0 · Cited by 155
Kimura, R., Devi, L., & Ohno, M. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06608.x · Cited by 147
Mann, D. M. A. (1983) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(83)90100-8 · Cited by 135
Jardanhazi‐Kurutz, D., Kummer, M. P., Terwel, D., Vogel, K., Dyrks, T., Thiele, A., & Heneka, M. T. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.02.001 · Cited by 135
Peskind, E. R., Tsuang, D. W., Bonner, L. T., Pascualy, M., Riekse, R. G., Snowden, M. B., Thomas, R. G., & Raskind, M. A. (2005) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000155067.16313.5e · Cited by 133
Hoogendijk, W. J. G., Pool, C. W., Troost, D., van Zwieten, E. J., & Swaab, D. F. (1995) · Brain · doi:10.1093/brain/118.1.131 · Cited by 132
Szabó, C., Haskó, G., Zingarelli, B., Nemeth, Z. H., Salzman, A. L., Kvetan, V., Pastores, S. M., & Vizi, E. S. (1997) · Immunology · doi:10.1046/j.1365-2567.1997.00137.x · Cited by 132
Norepinephrine Suppresses Inducible Nitric Oxide Synthase Activity in Rat Astroglial Cultures
Feinstein, D. L., Galea, E., & Reis, D. J. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb13425.x · Cited by 129
Non-Steroidal Anti-Inflammatory Drugs and Alzheimers Disease: The Epidemiological Evidence
Szekely, C. A., & Zandi, P. P. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791012026 · Cited by 116
Szot, P., White, S. S., Greenup, J. L., Leverenz, J. B., Peskind, E. R., & Raskind, M. A. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.01.031 · Cited by 110
Urano, T., & Tohda, C. (2010) · Phytotherapy Research · doi:10.1002/ptr.3183 · Cited by 103
L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug
Goldstein, D. S. (2006) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2006.00189.x · Cited by 94
Cole, G. M., & Frautschy, S. A. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791011991 · Cited by 85
Alterations in the locus coeruleus in dementias of Alzheimer's and Parkinson's disease
Chan‐Palay, V. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63839-x · Cited by 84
Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice
Guérin, D., Sacquet, J., Mandairon, N., Jourdan, F., & Didier, A. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.05.020 · Cited by 82
Madrigal, J. L. M., Kalinin, S., Richardson, J. C., & Feinstein, D. L. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04888.x · Cited by 77
Self-citationTraver, S., Marien, M. R., Martin, E., Hirsch, É. C., & Michel, P. P. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.022715 · Cited by 71
Increasing CNS Noradrenaline Reduces EAE Severity
Simonini, M. V., Polak, P. E., Sharp, A. J., McGuire, S. O., Galea, E., & Feinstein, D. L. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9182-2 · Cited by 69
Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice
O’Neil, J. N., Mouton, P. R., Tizabi, Y., Ottinger, M. A., Lei, D.-L., Ingram, D. K., & Manaye, K. F. (2007) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2007.05.008 · Cited by 68
O’Sullivan, J. B., Ryan, K. M., Harkin, A., & Connor, T. J. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.12.007 · Cited by 65
Mohs, R. C., Shiovitz, T. M., Tariot, P. N., Porsteinsson, A. P., Baker, K. D., & Feldman, P. D. (2009) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181aad585 · Cited by 59
Prakash, A., Zhang, H., & Pandey, S. C. (2008) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00650.x · Cited by 52
The PDAPP mouse model of Alzheimer's disease: Locus coeruleus neuronal shrinkage
German, D. C., Nelson, O. L., Liang, F., Liang, C., & Games, D. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20744 · Cited by 52
Szapacs, M. E., Numis, A. L., & Andrews, A. M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.04.010 · Cited by 49
Holm, P. C., Rodríguez, F. J., Kresse, A. E., Canals, J. M., Silos‐Santiago, I., & Arenas, E. (2003) · Development · doi:10.1242/dev.00565 · Cited by 45
Scullion, G. A., Kendall, D. A., Marsden, C. A., Sunter, D., & Pardon, M. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.09.002 · Cited by 44
Remy, S., Naveilhan, P., Brachet, P., & Neveu, I. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.1072 · Cited by 42
Effects of Noradrenaline on Neuronal NOS2 Expression and Viability
Madrigal, J. L. M., Russo, C. D., Gavrilyuk, V., & Feinstein, D. L. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.885 · Cited by 37
Benveniste, E. N., Huneycutt, B. S., Shrikant, P., & Ballestas, M. E. (1995) · Brain Behavior and Immunity · doi:10.1006/brbi.1995.1029 · Cited by 35
Beta-Amyloid-Dependent Expression of NOS2in Neurons: Prevention by an α2-Adrenergic Antagonist
Kalinin, S., Polak, P. E., Madrigal, J. L. M., Gavrilyuk, V., Sharp, A. J., Chauhan, N. B., Marien, M. R., Colpaert, F. C., & Feinstein, D. L. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.873 · Cited by 32
Self-citationPugh, P. L., Vidgeon-Hart, M., Ashmeade, T. E., Culbert, A. A., Seymour, Z. M., Perren, M. J., Joyce, F., Bate, S. T., Babin, A. L., Virley, D. J., et al. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-8 · Cited by 28
Research works printed but not linked: 1
- Holm, 2003, Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons, Development, 130, 3535, 10.1242/dev.00565 · DOI
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Metadata
- 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.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 33
- Issue
- 8
- Pages
- 1651-1663
- ISSN
- 0197-4580 (ISSN-L)
- 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
- 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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