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Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease

M Diez1, J Koistinaho, S J Dearmond

  • 1Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Proceedings of the National Academy of Sciences of the United States of America
|December 16, 1997
PubMed
Summary

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Prion disease significantly reduces neuropeptide Y Y2 receptors (Y2-Rs) in mouse hippocampus, impairing NPY binding. This dysfunction may contribute to clinical symptoms in scrapie.

Area of Science:

  • Neuroscience
  • Prion Disease Research
  • Molecular Biology

Background:

  • Neuropeptide Y (NPY) plays a crucial role in regulating neuronal function.
  • NPY Y2 receptors (Y2-Rs) are implicated in various neurological processes.
  • Prion diseases, like scrapie, cause neurodegeneration and synaptic dysfunction.

Purpose of the Study:

  • To investigate the impact of intracerebral prion inoculation on Y2-Rs in the mouse hippocampus.
  • To determine if prion accumulation affects Y2-R expression and function.

Main Methods:

  • Autoradiographic binding assays using monoiodinated peptide YY (PYY) and NPY agonists.
  • In situ hybridization to quantify Y2-R mRNA levels.
  • Study conducted in male CD-1 mice inoculated intracerebrally with prions.

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Main Results:

  • Significant down-regulation of PYY binding (85% in CA1, 50-65% in CA3) observed 110-140 days postinoculation.
  • Y2-R mRNA levels showed a slight, non-significant decrease in CA3 neurons.
  • Prion accumulation strongly inhibited NPY binding to Y2-Rs, primarily independent of mRNA levels.

Conclusions:

  • Scrapie prion protein accumulation in the hippocampus severely impairs NPY binding to Y2-Rs.
  • Reduced Y2-R function, rather than decreased receptor expression, likely contributes to hippocampal circuit dysfunction.
  • This Y2-R dysfunction may play a role in the clinical manifestations of mouse scrapie.