Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease.
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.
Diez
M
M
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Koistinaho
J
J
Dearmond
S J
SJ
Groth
D
D
Prusiner
S B
SB
Hökfelt
T
T
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D006624:Hippocampus / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*
D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor