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Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.
J Pineal Res 2009; 47(1):82-96JP

Abstract

The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of Alzheimer disease.

Authors+Show Affiliations

Florida State University College of Medicine, Tallahassee, FL, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19538338

Citation

Olcese, James M., et al. "Protection Against Cognitive Deficits and Markers of Neurodegeneration By Long-term Oral Administration of Melatonin in a Transgenic Model of Alzheimer Disease." Journal of Pineal Research, vol. 47, no. 1, 2009, pp. 82-96.
Olcese JM, Cao C, Mori T, et al. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res. 2009;47(1):82-96.
Olcese, J. M., Cao, C., Mori, T., Mamcarz, M. B., Maxwell, A., Runfeldt, M. J., ... Arendash, G. W. (2009). Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. Journal of Pineal Research, 47(1), pp. 82-96. doi:10.1111/j.1600-079X.2009.00692.x.
Olcese JM, et al. Protection Against Cognitive Deficits and Markers of Neurodegeneration By Long-term Oral Administration of Melatonin in a Transgenic Model of Alzheimer Disease. J Pineal Res. 2009;47(1):82-96. PubMed PMID: 19538338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. AU - Olcese,James M, AU - Cao,Chuanhai, AU - Mori,Takashi, AU - Mamcarz,Malgorzata B, AU - Maxwell,Anne, AU - Runfeldt,Melissa J, AU - Wang,Li, AU - Zhang,Chi, AU - Lin,Xiaoyang, AU - Zhang,Guixin, AU - Arendash,Gary W, Y1 - 2009/06/17/ PY - 2009/6/23/entrez PY - 2009/6/23/pubmed PY - 2009/9/4/medline SP - 82 EP - 96 JF - Journal of pineal research JO - J. Pineal Res. VL - 47 IS - 1 N2 - The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of Alzheimer disease. SN - 1600-079X UR - https://www.unboundmedicine.com/medline/citation/19538338/Protection_against_cognitive_deficits_and_markers_of_neurodegeneration_by_long_term_oral_administration_of_melatonin_in_a_transgenic_model_of_Alzheimer_disease_ L2 - https://doi.org/10.1111/j.1600-079X.2009.00692.x DB - PRIME DP - Unbound Medicine ER -