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Memory improvement in the AβPP/PS1 mouse model of familial Alzheimer's disease induced by carbamylated-erythropoietin is accompanied by modulation of synaptic genes
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Neuroprotection of erythropoietin (EPO) following long-term administration is hampered by the associated undesirable effects on hematopoiesis and body weight. For this reason, we tested carbamylated-EPO (CEPO), which has no effect on erythropoiesis, and compared it with EPO in the AβPP/PS1 mouse model of familial Alzheimer's disease. Groups of 5-month-old wild type (WT) and transgenic mice received chronic treatment consisting of CEPO (2,500 or 5,000 UI/kg) or EPO (2,500 UI/kg) 3 days/week for 4 weeks. Memory at the end of treatment was assessed with the object recognition test. Microarray analysis and quantitative-PCR were used for gene expression studies. No alterations in erythropoiesis were observed in CEPO-treated WT and AβPP/PS1 transgenic mice. EPO and CEPO improved memory in AβPP/PS1 animals. However, only EPO decreased amyloid-β (Aβ) plaque burden and soluble Aβ40. Microarray analysis of gene expression revealed a limited number of common genes modulated by EPO and CEPO. CEPO but not EPO significantly increased gene expression of dopamine receptors 1 and 2, and adenosine receptor 2a, and significantly down-regulated adrenergic receptor α1D and gastrin releasing peptide. CEPO treatment resulted in higher protein levels of dopamine receptors 1 and 2 in WT and AβPP/PS1 animals, whereas the adenosine receptor 2a was reduced in WT animals. The present results suggest that the improved behavior observed in AβPP/PS1 transgenic mice after CEPO treatment may be mediated, at least in part, by the observed modulation of the expression of molecules involved in neurotransmission.
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ARMAND-UGÓN, Mercedes, ASO PÉREZ, Ester, MORENO CASTRO, Jesús, RIERA I CODINA, Miquel, SÀNCHEZ, Àlex (sànchez pla), VEGAS LOZANO, Esteban, FERRER, Isidro (ferrer abizanda). Memory improvement in the AβPP/PS1 mouse model of familial Alzheimer's disease induced by carbamylated-erythropoietin is accompanied by modulation of synaptic genes. _Journal of Alzheimer's Disease_. 2015. Vol. 45, núm. 2, pàgs. 407-421. [consulta: 28 de gener de 2026]. ISSN: 1387-2877. [Disponible a: https://hdl.handle.net/2445/67988]