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Título:
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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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Autor/a:
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Armand-Ugón, Mercedes; Asó, Ester; Moreno Castro, Jesús; Riera i Codina, Miquel; Sànchez, Àlex (Sànchez Pla); Vegas Lozano, Esteban; Ferrer, Isidro (Ferrer Abizanda)
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Abstract:
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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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Materia(s):
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-Malaltia d'Alzheimer
-Receptors de neurotransmissors
-Eritropoetina
-Alzheimer's disease
-Neurotransmitter receptors
-Erythropoietin |
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Derechos:
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(c) Armand-Ugón, Mercedes et al., 2015
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Tipo de documento:
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Artículo
Artículo - Versión publicada |
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Editor:
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IOS Press
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Compartir:
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