AMPA receptor regulation and LTP in the hippocampus of young and aged apolipoprotein E-deficient mice

Neurobiol Aging. 2001 Jan-Feb;22(1):9-15. doi: 10.1016/s0197-4580(00)00177-9.

Abstract

In the present study, modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors by phosphatidylserine (PS) and synaptic plasticity were investigated in the hippocampus of young (4-month-old) and aged (18-month-old) apolipoprotein E (apoE)-deficient mice. Qualitative as well as quantitative analysis of brain sections in both young and aged apoE-deficient mice did not reveal any substantial changes of AMPA receptor binding in the various hippocampal regions, compared to age-matched controls. Nevertheless, enhancement of AMPA receptor binding elicited by PS treatment was found to be abolished in most hippocampal regions of young apoE-deficient mice, while modulation of AMPA receptors by this phospholipid was not significantly altered in the hippocampal formation of aged apoE-deficient animals. At the electrophysiological level, long-term potentiation (LTP) induced by theta burst stimulation was lower in area CA1 of the hippocampus of young, but not aged, apoE-deficient mice compared to age-matched controls. These results confirm that apoE is important for AMPA receptor regulation and LTP expression in the hippocampal formation. However, the presence of LTP in aged apoE-deficient animals, together with apparent recovery of the PS action on AMPA receptors, suggests that aged apoE-knockout mice possess compensatory mechanisms that reduce biochemical and electrophysiological alterations of glutamatergic neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Apolipoproteins E / deficiency*
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylserines / pharmacology
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism*

Substances

  • Apolipoproteins E
  • Phosphatidylserines
  • Receptors, AMPA