The substrates of memory: defects, treatments, and enhancement.

Full 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.

Author information

Author/s: Lynch, Gary (G); Rex, Christopher S (CS); Chen, Lulu Y (LY); Gall, Christine M (CM);

Affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine CA, United States.

Grants: AG00258 (Agency:NIA NIH HHS) ; NS045260 (Agency:NINDS NIH HHS) ; NS051823 (Agency:NINDS NIH HHS) ; NS37799 (Agency:NINDS NIH HHS) ; P01 NS045260-03 (Agency:NINDS NIH HHS) ; P01 NS045260-04 (Agency:NINDS NIH HHS) ; R01 NS037799-06 (Agency:NINDS NIH HHS) ; R01 NS037799-07 (Agency:NINDS NIH HHS) ; R01 NS051823-07 (Agency:NINDS NIH HHS) ; T32 AG000096-21 (Agency:NIA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Review

Journal: European journal of pharmacology (Eur J Pharmacol), published in Netherlands. (Language: eng)

Reference: 2008-May; vol 585 (issue 1) : pp 2-13

Dates: Created 2008/04/28; Completed 2008/10/31; Revised 2009/05/07;

PMID: 18374328, status: MEDLINE (last retrieval date: 5/8/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.