title: Memory Improvement in the AβPP/PS1 Mouse Model of Familial Alzheimer’s Disease Induced by Carbamylated-Erythropoietin is Accompanied by Modulation of Synaptic Genes.
abstract: 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 U I/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 Aβ(40). 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 1D 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.
authors: Institut de Neuropatologia, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, L’Hospitalet de Llobregat, Spain. marmand@idibell.cat
authors: Mercedes
authors: M
authors: Armand-Ugón
authors: Ester
authors: E
authors: Aso
authors: Jesús
authors: J
authors: Moreno
authors: Miquel
authors: M
authors: Riera-Codina
authors: Alex
authors: A
authors: Sánchez
authors: Esteban
authors: E
authors: Vegas
authors: Isidre
authors: I
authors: Ferrer
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D017983:Receptors, Catecholamine / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D017983:Receptors, Catecholamine; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C488171:carbamylated erythropoietin; D004921:Erythropoietin; D019886:Gastrin-Releasing Peptide