NR ADKF
AU Diez,M.; Koistinaho,J.; DeArmond,S.J.; Groth,D.; Prusiner,S.B.; Hokfelt,T.
TI Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease
QU Proceedings of the National Academy of Sciences of the United States of America 1997 Nov 25; 94(24): 13267-72
PT journal article
AB Using autoradiographic binding methodology with monoiodinated peptide YY together with the agonists neuropeptide Y (NPY) and NPY (13-36), as well as in situ hybridization with oligonucleotide probes complementary to the NPY Y2 receptor (Y2-R) mRNA, we have studied whether or not intracerebral prion inoculation affects Y2-Rs in male CD-1 mice. Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation. In the CA3 stratum radiatum, where the mossy fibers from the dentate granule cells project, there was a significant decrease in PYY binding at 110-120 days. Y2-R mRNA, moderately expressed both in the CA1 and CA3 pyramidal cell layers and the granule cell layer in the dentate gyrus, showed a slight, but not significant, decrease in CA3 neurons 130 days postinoculation. The results indicate that the accumulation of the scrapie prion protein in the CA1-3 region strongly inhibits NPY binding at the Y2-Rs, which, however, is only marginally due to reduced Y2-R mRNA expression. The loss of the ability of NPY to bind to inhibitory Y2-Rs may cause dysfunction of hippocampal circuits and may contribute to the clinical symptoms in mouse scrapie.
MH Animal; Autoradiography; Binding Sites; Hippocampus/*metabolism; In Situ Hybridization; Male; Mice; Neuropeptide Y/metabolism; RNA, Messenger/genetics/metabolism; Receptors, Neuropeptide Y/genetics/*metabolism; Scrapie/*metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
SP englisch
PO USA