A role of insulin-like growth factor 1 in beta amyloid-induced disinhibition of hippocampal neurons

Neurosci Lett. 2005 Aug;384(1-2):93-7. doi: 10.1016/j.neulet.2005.04.063.

Abstract

In the present study we investigated the effects of beta amyloid (Abeta) on inhibitory synaptic transmission in the cultured hippocampal neurons using whole-cell patch-clamp recordings and immunocytochemistry, and examined the role of insulin-like growth factor 1 (IGF-1). Incubation with 4 microM Abeta25-35 for 24 h significantly decreased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), but had no effect on the mean amplitude. Pretreatment with 10 ng/ml IGF-1 for 24h prior to Abeta25-35 exposure blocked Abeta-induced disinhibition of hippocampal neurons. The frequency and mean amplitude of miniature IPSC (mIPSCs) were not significantly affected by Abeta. The rise and decay kinetics of sIPSCs and mIPSCs were similar for the control and Abeta25-35-treated hippocampal neurons. Immunocytochemistry showed no changes in the ratio of gamma-aminobutyric acid (GABA) positive cells subsequent to treatment with Abeta, or IGF-1. Together these data suggest that Abeta-induced the disinhibition in cultured hippocampal neurons, whereas IGF-1 could block this effect.

Publication types

  • Comparative Study

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Cell Count / methods
  • Drug Interactions
  • Embryo, Mammalian
  • Female
  • Hippocampus / cytology*
  • Immunohistochemistry / methods
  • Insulin-Like Growth Factor Binding Protein 1 / pharmacology*
  • Male
  • Membrane Potentials / drug effects
  • Neural Inhibition / drug effects*
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques / methods
  • Peptide Fragments / toxicity*
  • Pregnancy
  • Rats
  • Synaptic Transmission / drug effects*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amyloid beta-Peptides
  • Insulin-Like Growth Factor Binding Protein 1
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • gamma-Aminobutyric Acid