Memory impairment induced by chronic intracerebroventricular infusion of beta-amyloid (1-40) involves downregulation of protein kinase C

Ana Olariu, Kiyofumi Yamada, Takayoshi Mamiya, Vasile Hefco, Toshitaka Nabeshima

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Signaling pathways underlying the cognitive deficit of the Alzheimer's disease (AD) are not completely understood. Protein kinase C (PKC), a major neuronal protein plays a critical role in cellular signal transduction and it is known to be subjected to modulation in AD. We showed previously that, chronic infusion of β-amyloid (1-40) into rat cerebroventricle leads to deficit in spatial and non-spatial memory formation. As an attempt to identify the cellular correlates of the memory deficit, in the present study we investigated the PKC activation in different brain areas. Chronic infusion of β-amyloid (1-40) for 14 days into the rat cerebroventricle decreased the activity of soluble protein kinase C (PKC) in the hippocampus. Subcellular translocation of PKC to membrane fraction in hippocampal slices of rats treated with β-amyloid (1-40) was completely abolished under acute stimulation with 0.5 μM phorbol-dibutyrate (PDBu). We also reported a decreased affinity (kD) for PDBu binding in the hippocampus, cerebral cortex and striatum. The total number of binding sites for PDBu (Bmax) was increased, in the three brain areas analyzed on the day 14, but the changes were not statistically significant. Our data indicate that chronic accumulation of β-amyloid (1-40) into the rat brain reduced activation of PKC, effect that would substantially contribute to the memory deficit found in these animals.

Original languageEnglish
Pages (from-to)278-286
Number of pages9
JournalBrain Research
Volume957
Issue number2
DOIs
Publication statusPublished - 13-12-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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