Journal of Alzheimer's disease, 2015-01, Vol.45 (2), p.407
2015
Details
- Autor(en) / Beteiligte
- Titel
- Memory Improvement in the AβPP/PS1 Mouse Model of Familial Alzheimer’s Disease Induced by Carbamylated-Erythropoietin is Accompanied by Modulation of Synaptic Genes
- Ist Teil von
- Journal of Alzheimer's disease, 2015-01, Vol.45 (2), p.407
- Ort / Verlag
- Netherlands
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1875-8908DOI: 10.3233/JAD-141389Titel-ID: cdi_pubmed_primary_25790933
- Format
- –
- Schlagworte
- Alzheimer Disease - complications, Alzheimer Disease - genetics, Amyloid beta-Peptides - metabolism, Amyloid beta-Protein Precursor - genetics, Animals, Body Weight - drug effects, Body Weight - genetics, Disease Models, Animal, Erythropoietin - analogs & derivatives, Erythropoietin - therapeutic use, Gastrin-Releasing Peptide - metabolism, Gene Expression Regulation - drug effects, Gene Expression Regulation - genetics, Humans, Male, Memory Disorders - drug therapy, Memory Disorders - etiology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation - genetics, Peptide Fragments - metabolism, Presenilin-1 - genetics, Receptors, Catecholamine - metabolism, Synapses - genetics, Synapses - metabolism, Time Factors