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

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.

• Authors: Soon-Tae Lee, Kon Chu, Jung-Eun Park, Keun-Hwa Jung, Daejong Jeon, Ji-Youn Lim, Sang Kun Lee, Manho Kim, Jae-Kyu Roh
• Journal: Journal of neurochemistry (J Neurochem) Vol. 120 Issue 1 Pg. 115-24 (Jan 2012) ISSN: 1471-4159 [Electronic] England
• PMID: 22004348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Chemical References

• Amyloid beta-Peptides
• Glycation End Products, Advanced
• Synaptophysin
• Erythropoietin

Topics

• Amyloid beta-Peptides (metabolism)
• Animals
• Blotting, Western
• Brain Chemistry (genetics)
• Capillaries (growth & development, physiology)
• Cells, Cultured
• Cues
• Endothelial Cells (metabolism)
• Endothelium, Vascular (growth & development, physiology)
• Enzyme-Linked Immunosorbent Assay
• Erythropoietin (genetics, physiology)
• Fear (psychology)
• Glycation End Products, Advanced (metabolism)
• Memory (drug effects)
• Mice
• Mice, Transgenic
• Neovascularization, Physiologic (genetics, physiology)
• Plaque, Amyloid (pathology)
• Synaptophysin (biosynthesis)