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Amyloid precursor protein mRNA encoding the Kunitz protease inhibitor domain is increased by kainic acid-induced

D A Willoughby1, S A Johnson, G M Pasinetti

  • 1Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.

Experimental Neurology
|December 1, 1992
PubMed

Insights

Kainic acid seizures increase Kunitz protease inhibitor (KPI) mRNA in rat hippocampus. Anticonvulsants block this effect, suggesting seizures alter amyloid precursor protein (APP) RNA processing.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The amyloid precursor protein (APP) gene undergoes alternative splicing.
  • A specific exon encodes a Kunitz protease inhibitor (KPI) domain within APP mRNA variants.

Purpose of the Study:

  • To investigate the effect of kainic acid-induced seizures on KPI mRNA expression in the rat hippocampus.
  • To determine if anticonvulsant pretreatment affects seizure-induced changes in KPI mRNA.

Main Methods:

  • In situ hybridization was used to detect KPI mRNA localization and levels.
  • Kainic acid was administered to induce seizures in rats.
  • Pentobarbital was used as a pretreatment to assess its effect on KPI mRNA induction.

Main Results:

  • Kainic acid administration selectively increased KPI mRNA levels in the rat hippocampus.
  • KPI mRNA induction was observed in hippocampal neuronal layers 11-12 hours post-seizure onset.
  • Pentobarbital pretreatment blocked the kainate-induced elevation of KPI-containing APP-770 mRNA.

Conclusions:

  • Kainate-induced seizures alter APP RNA stability and/or processing in hippocampal neurons.
  • The induction of KPI mRNA is linked to seizure activity and can be modulated by anticonvulsants.

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