The substrates of memory: defects, treatments, and enhancement

Eur J Pharmacol. 2008 May 6;585(1):2-13. doi: 10.1016/j.ejphar.2007.11.082. Epub 2008 Mar 4.

Abstract

Recent work has added strong support to the long-standing hypothesis that the stabilization of both long-term potentiation and memory requires rapid reorganization of the spine actin cytoskeleton. This development has led to new insights into the origins of cognitive disorders, and raised the possibility that a diverse array of memory problems, including those associated with diabetes, reflect disturbances to various components of the same mechanism. In accord with this argument, impairments to long-term potentiation in mouse models of Huntington's disease and in middle-aged rats have both been linked to problems with modulatory factors that control actin polymerization in spine heads. Complementary to the common mechanism hypothesis is the idea of a single treatment for addressing seemingly unrelated memory diseases. First tests of the point were positive: Brain-Derived Neurotrophic Factor (BDNF), a potent activator of actin signaling cascades in adult spines, rescued potentiation in Huntington's disease mutant mice, middle-aged rats, and a mouse model of Fragile-X syndrome. A similar reversal of impairments to long-term potentiation was obtained in middle-aged rats by up-regulating BDNF production with brief exposures to ampakines, a class of drugs that positively modulate AMPA-type glutamate receptors. Work now in progress will test if chronic elevation of BDNF enhances memory in normal animals.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Actins / physiology
  • Aging / physiology
  • Animals
  • Brain / physiopathology
  • Brain-Derived Neurotrophic Factor / physiology
  • Cytoskeleton / physiology
  • Dendritic Spines / physiology
  • Fragile X Syndrome / physiopathology
  • Humans
  • Huntington Disease / physiopathology
  • Learning / physiology
  • Long-Term Potentiation*
  • Memory / drug effects
  • Memory / physiology*
  • Memory Disorders* / drug therapy
  • Memory Disorders* / physiopathology
  • Nootropic Agents / pharmacology
  • Nootropic Agents / therapeutic use
  • Synapses / physiology

Substances

  • Actins
  • Brain-Derived Neurotrophic Factor
  • Nootropic Agents