Group I mGluR signaling in BSE-infected bovine-PrP transgenic mice.
Abnormalities of synapses and impaired synaptic transmission appear to be crucial in the pathogenesis of prion diseases. Excitotoxic mechanisms have been postulated as a major cause of neurodegeneration in these conditions. In this line, previous studies have shown abnormal group 1 metabotropic glutamate receptor signaling in Creutzfeldt-Jakob disease (CJD). In the present study, we have examined this pathway by western blotting in the cerebral cortex of bovine-spongiform encephalopathy (BSE)-infected bovine-PrP transgenic mice at different days post-inoculation (dpi). Activation of post-synaptic metabotropic glutamate receptor 1 (mGluR1) promotes phospholipase Cbeta1 (PLCbeta1) activation which may activate, in turn, protein kinase C (PKC), which regulates gene expression. Densitometric analysis of the western blot bands revealed no differences in the protein levels of (mGluR1) through time, but demonstrated decreased levels of PLCbeta1 and protein kinase C delta (nPKCdelta) at 270dpi, at the time when mice showed neurological deficits accompanied by neuropathological changes and PrPres deposition in the brain. The present results show, for the first time impairment of the mGluR1/PLCbeta1/PKCdelta pathway signaling with disease-progression in a murine model of BSE.
Rodríguez
Agustín
A
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Spain.
Martín
Mairena
M
Albasanz
José Luís
JL
Barrachina
Marta
M
Espinosa
Juan Carlos
JC
Torres
Juan María
JM
Ferrer
Isidre
I
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D054799:Phospholipase C beta; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; D011328:Prions; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D051745:Protein Kinase C-delta; D010738:Type C Phospholipases; D054799:Phospholipase C beta