Erythropoietin improves memory function with reducing endothelial dysfunction and amyloid-beta burden in Alzheimer's disease models

Soon Tae Lee, Kon Chu, Jung Eun Park, Keun Hwa Jung, Daejong Jeon, Ji Youn Lim, Sang Kun Lee, Manho Kim, Jae Kyu Roh

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Neurovascular degeneration contributes to the pathogenesis of Alzheimer's disease (AD). Because erythropoietin (EPO) promotes endothelial regeneration, we investigated the therapeutic effects of EPO in animal models of AD. In aged Tg2576 mice, EPO receptors (EPORs) were expressed in the cortex and hippocampus. Tg2576 mice were treated with daily injection of EPO (5000 IU/kg/day) for 5 days. At 14 days, EPO improved contextual memory as measured by fear-conditioning test. EPO enhanced endothelial proliferation and the level of synaptophysin expression in the brain. EPO also increased capillary density, and decreased the level of the receptor for advanced glycation endproducts (RAGE) in the brain, while decreasing in the amount of amyloid plaque and amyloid-β (Aβ). In cultured human endothelial cells, EPO enhanced angiogenesis and suppressed the expression of the RAGE. These results show that EPO improves memory and ameliorates endothelial degeneration induced by Aβ in AD models. This pre-clinical evidence suggests that EPO may be useful for the treatment of AD.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalJournal of Neurochemistry
Volume120
Issue number1
DOIs
StatePublished - 1 Jan 2012

Fingerprint

Erythropoietin
Amyloid
Alzheimer Disease
Data storage equipment
Brain
Erythropoietin Receptors
Synaptophysin
Endothelial cells
Amyloid Plaques
Therapeutic Uses
Fear
Regeneration
Hippocampus
Animals
Endothelial Cells
Animal Models
Injections

Keywords

  • Alzheimer's disease
  • Tg2576
  • amyloid-beta
  • angiogenesis
  • erythropoietin
  • receptor for advanced glycation endproducts

Cite this

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abstract = "Neurovascular degeneration contributes to the pathogenesis of Alzheimer's disease (AD). Because erythropoietin (EPO) promotes endothelial regeneration, we investigated the therapeutic effects of EPO in animal models of AD. In aged Tg2576 mice, EPO receptors (EPORs) were expressed in the cortex and hippocampus. Tg2576 mice were treated with daily injection of EPO (5000 IU/kg/day) for 5 days. At 14 days, EPO improved contextual memory as measured by fear-conditioning test. EPO enhanced endothelial proliferation and the level of synaptophysin expression in the brain. EPO also increased capillary density, and decreased the level of the receptor for advanced glycation endproducts (RAGE) in the brain, while decreasing in the amount of amyloid plaque and amyloid-β (Aβ). In cultured human endothelial cells, EPO enhanced angiogenesis and suppressed the expression of the RAGE. These results show that EPO improves memory and ameliorates endothelial degeneration induced by Aβ in AD models. This pre-clinical evidence suggests that EPO may be useful for the treatment of AD.",
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Erythropoietin improves memory function with reducing endothelial dysfunction and amyloid-beta burden in Alzheimer's disease models. / Lee, Soon Tae; Chu, Kon; Park, Jung Eun; Jung, Keun Hwa; Jeon, Daejong; Lim, Ji Youn; Lee, Sang Kun; Kim, Manho; Roh, Jae Kyu.

In: Journal of Neurochemistry, Vol. 120, No. 1, 01.01.2012, p. 115-124.

Research output: Contribution to journalArticle

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AU - Lim, Ji Youn

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AU - Kim, Manho

AU - Roh, Jae Kyu

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