Research article summary (published 2007):

Enhancement of learning and memory after activation of cerebral Rho GTPases.

Full 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.

Author information

Author/s: Diana, Giovanni (G); Valentini, Giovanni (G); Travaglione, Sara (S); Falzano, Loredana (L); Pieri, Massimo (M); Zona, Cristina (C); Meschini, Stefania (S); Fabbri, Alessia (A); Fiorentini, Carla (C);

Affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. giovanni.diana(-atsign-)iss.it

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2007-Jan; vol 104 (issue 2) : pp 636-41

Dates: Created 2007/01/10; Completed 2007/02/16; Revised 2008/11/20;

PMID: 17202256, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actins - metabolism Animals Bacterial Toxins - toxicity Brain - drug effects; enzymology Cells, Cultured Conditioning (Psychology) - drug effects; physiology Cytotoxins - toxicity Dendrites - drug effects; metabolism; ultrastructure Enzyme Activation Escherichia coli Proteins - toxicity Fear - drug effects; physiology

Fear - drug effects; physiology Hippocampus - drug effects; physiology Learning - drug effects; physiology Male Memory - drug effects; physiology Mice Mice, Inbred C57BL Neurons - drug effects; metabolism; ultrastructure Spatial Behavior - drug effects; physiology Synaptic Transmission - drug effects rho GTP-Binding Proteins - metabolism

Associated Chemicals: Actins (0) ; Bacterial Toxins (0) ; Cytotoxins (0) ; Escherichia coli Proteins (0) ; cytotoxic necrotizing factor type 1 (106803-33-2) ; rho GTP-Binding Proteins (EC 3.6.5.2)

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