ApoE isoform-dependent changes in hippocampal synaptic function.

Published online

Journal Article

The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR) mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP) is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.

Full Text

Duke Authors

Cited Authors

  • Korwek, KM; Trotter, JH; Ladu, MJ; Sullivan, PM; Weeber, EJ

Published Date

  • May 27, 2009

Published In

Volume / Issue

  • 4 /

Start / End Page

  • 21 -

PubMed ID

  • 19725929

Pubmed Central ID

  • 19725929

Electronic International Standard Serial Number (EISSN)

  • 1750-1326

Digital Object Identifier (DOI)

  • 10.1186/1750-1326-4-21

Language

  • eng

Conference Location

  • England