Enhancement of learning and memory after activation of cerebral Rho GTPases

Giovanni Diana, Giovanni Valentini, Sara Travaglione, Loredana Falzano, Massimo Pieri, Cristina Zona, Stefania Meschini, Alessia Fabbri, Carla Fiorentini

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism whereby the morphology and connectivity of the dendritic tree is regulated depends on an actin dynamics that, in turn, is controlled by Rho GTPases, a family of small GTP-binding proteins encompassing Rho, Rac, and Cdc42 subfamilies. Cytotoxic necrotizing factor 1 (CNF1), a protein toxin from Escherichia coli. constitutively activates Rho GTPases, thus leading to remodeling of the actin cytoskeleton in intact cells. Here, we show that the modulation of cerebral RhoA and Rac1 activity induced by CNF1 in mice leads to (i) rearrangement of cerebral actin cytoskeleton, (ii) enhanced neurotransmission and synaptic plasticity, and (iii) improved learning and memory in various behavioral tasks. The effects persist for weeks and are not observed in mice treated with a recombinant CNF1, in which the enzymatic activity was abolished by substituting serine to cysteine at position 866. The results suggest that learning ability can be improved through pharmacological manipulation of neural connectivity.

Original languageEnglish
Pages (from-to)636-641
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number2
DOIs
Publication statusPublished - Jan 9 2007

Keywords

  • Bacterial toxins
  • Brain
  • Cytotoxic necrotizing factor 1
  • Dendritic spines
  • Drug therapy

ASJC Scopus subject areas

  • Genetics
  • General

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