NR AWMO
AU Rodriguez,A.; Martin,M.; Albasanz,J.L.; Barrachina,M.; Torres,J.M.; Espinosa,J.C.; Ferrer,I.
TI Adenosine A1 receptor expression and activity is increased in the cerebral cortex in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP mice
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-45
PT Konferenz-Poster
AB Creutzfeldt-Jakob's disease (CJD) is the most prevalent human TSE, whereas scrapie and bovine spongiform encephalopathy (BSE) are the most common animal prion diseases. Adenosine function is mediated by adenosine receptors (ADRs), which are categorized into four types: A1, A2A, A2B and A3. A1Rs are G-protein-coupled receptors which induce the inhibition of adenylyl cyclase (AC) activity. In the present work, we have examined, by western blotting, the expression levels of A1Rs in the frontal cortex of 12 patients with CJD and 6 age-matched controls, and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice (BoPrP-Tg110 mice) at different post-incubation times to address modifications in A1Rs with disease progression. A significant increase in the expression levels of A1Rs was found, by immunohistochemistry and later by Western blotting, in the cerebral cortex in CJD, and in the murine BSE model at advanced stages of the disease and coincidental with the appearance of PrPres expression. In addition, the activity of A1Rs was analyzed by in vitro assays with isolated membranes of the frontal cortex in CJD. Increased activity of the receptor, as revealed by the decreased forskolin-stimulated cAMP production in response to the A1R agonists cyclohexyladenosine (CHA) and cyclopentyladenosine (CPA), was observed in CJD cases when compared with controls. These findings contrast with reduced signaling of group I metabotropic glutamate receptors in prion disaeses. Finally, mRNA A1R levels were similar in CJD and control cases, thus suggesting abnormal A1R turnover or disregulation of raft-associate signaling pathways in CJD. These results show, for the first time, sensitization of A1Rs in prion diseases.
AD A. Rodríguez, M. Barrachina: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Spain; M. Martin, J.L. Albasanz: Departamento de Química Inorgánica, Orgánica y Bioquímica,Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real (MM, JLA), Spain; J.M. Torres, J.C. Espinosa: Centro de Investigación en Sanidad Animal (CISA), INIA, 28130 Valdeolmos, Madrid (JCE, JMT), Spain; I. Ferrer: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Spain, and Facultat de Medicina, Universitat de Barcelona, 08907Hospitalet de Llobregat, Spain. E-mail: 8082ifa@comb.es
SP englisch
PO Italien