4.5 Article

Effects of Fish Oil Combined with Selenium and Zinc on Learning and Memory Impairment in Aging Mice and Amyloid Precursor Protein Processing

期刊

BIOLOGICAL TRACE ELEMENT RESEARCH
卷 199, 期 5, 页码 1855-1863

出版社

SPRINGERNATURE
DOI: 10.1007/s12011-020-02280-y

关键词

Amyloid precursor protein; Docosahexaenoic acid; Eicosapentaenoic acid; Learning and memory; Selenium; Zinc

资金

  1. Research Foundation of TCM Science and Technology Project of Jilin Province [2018-135]
  2. Jilin Provincial Education Department [JJKH20200532KJ]
  3. National Science Foundation of China [81660142]
  4. China Scholarship Council [2016-3192]

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Fish oil combined with selenium and zinc has been shown to improve learning and memory impairment in an aging mouse model. The combination treatment also inhibited APP processing and reduced Aβ content in cells, suggesting a potential therapeutic strategy for Alzheimer's disease.
Alzheimer's disease is characterized by the aggregation of amyloid-beta (A beta) peptide into plaques and neurofibrillary tangles. A beta peptide is generated by the cleavage of the beta-amyloid precursor protein (APP) by beta- and gamma-secretase. The present study was conducted to investigate the effects of fish oil (or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), selenium, and zinc on learning and memory impairment in an aging mouse model and on APP. We performed the Morris water maze and platform recorder tests on male Kunming mice (10/group) grouped as control andd-galactose-induced aging model mice treated with vehicle, fish oil, fish oil + selenium, fish oil + selenium + zinc, and positive control (red ginseng extract). Fish oil + zinc + selenium for 7 weeks significantly improved learning and memory impairments in aging model animals in the Morris water maze and platform recorder tests, as evidenced by shortened incubation periods and number of errors. In vitro analysis of A beta(1-40)content in APP695-transfected CHO cells revealed a decrease after treatment with EPA, DHA, and their combinations with selenium or selenium and zinc. Assaying beta- and gamma-secretase activities revealed a decrease in PC(12)cells and mouse serum as well as a decrease in beta-site APP-cleaving enzyme 1 and presenilin 1 protein levels in the PC(12)cells and mouse serum. Taken together, our results show that fish oil combined with selenium and zinc inhibited APP processing and alleviated learning and memory impairment in a mouse model of aging.

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