Brain-derived neurotrophic factor antisense oligonucleotide impairs memory retention and inhibits long-term potentiation in rats

Neuroscience. 1998 Feb;82(4):957-67. doi: 10.1016/s0306-4522(97)00325-4.

Abstract

We have examined the relationship between brain-derived neurotrophic factor gene expression in the hippocampus and memory retention as well as long-term potentiation of rats. One-way inhibitory avoidance learning was adopted as the behavioural paradigm. Results revealed that brain-derived neurotrophic factor messenger RNA levels in the dentate gyrus of the hippocampus were markedly increased at 1 h, 3 h and 6 h post-training in rats showing good retention performance when compared with the poor retention controls. Direct injection of brain-derived neurotrophic factor antisense oligonucleotide into the dentate gyrus of the hippocampus before memory consolidation takes place markedly impaired retention performance in rats. It also significantly decreased brain-derived neurotrophic factor messenger RNA level in the dentate gyrus. The same antisense treatment also markedly reduced the amplitude and slope of excitatory postsynaptic potential as well as the brain-derived neurotrophic factor messenger RNA level in the dentate gyrus. These results suggest that hippocampal brain-derived neurotrophic factor gene expression plays an important role in the memory consolidation process and in the expression of long-term potentiation in rats. These results provide the first evidence to relate brain-derived neurotrophic factor gene expression and memory function in vertebrates. It further suggests that brain-derived neurotrophic factor gene expression is involved in behavioural plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Brain-Derived Neurotrophic Factor / genetics*
  • Electric Stimulation
  • Electrophysiology
  • Hypoxanthine Phosphoribosyltransferase / biosynthesis
  • Long-Term Potentiation / drug effects*
  • Male
  • Memory / drug effects*
  • Motor Activity / drug effects
  • Oligonucleotides, Antisense / pharmacology*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Brain-Derived Neurotrophic Factor
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Hypoxanthine Phosphoribosyltransferase