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.

Diana, G., Valentini, G., Travaglione, S., Falzano, L., Pieri, M., Zona, C., et al. (2007). Enhancement of learning and memory after activation of cerebral Rho GTPases. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104(2), 636-641 [10.1073/pnas.0610059104].

Enhancement of learning and memory after activation of cerebral Rho GTPases

PIERI, MASSIMO;ZONA, CRISTINA;FABBRI, ANDREA;
2007-01-01

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.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09 - FISIOLOGIA
English
Bacterial toxins; Brain; Cytotoxic necrotizing factor 1; Dendritic spines; Drug therapy
actin; cysteine; cytotoxic necrotizing factor 1; protein Cdc42; Rac1 protein; recombinant cytotoxic necrotizing factor 1; recombinant protein; Rho guanine nucleotide binding protein; RhoA guanine nucleotide binding protein; serine; amino acid substitution; animal experiment; animal tissue; article; conditioning; controlled study; dendrite; enzyme activation; Escherichia coli; learning; memory; mouse; nerve cell network; nerve cell plasticity; neurotransmission; nonhuman; priority journal; Actins; Animals; Bacterial Toxins; Brain; Cells, Cultured; Conditioning (Psychology); Cytotoxins; Dendrites; Enzyme Activation; Escherichia coli Proteins; Fear; Hippocampus; Learning; Male; Memory; Mice; Mice, Inbred C57BL; Neurons; rho GTP-Binding Proteins; Spatial Behavior; Synaptic Transmission; Bacteria (microorganisms); Escherichia coli; Mus
Diana, G., Valentini, G., Travaglione, S., Falzano, L., Pieri, M., Zona, C., et al. (2007). Enhancement of learning and memory after activation of cerebral Rho GTPases. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104(2), 636-641 [10.1073/pnas.0610059104].
Diana, G; Valentini, G; Travaglione, S; Falzano, L; Pieri, M; Zona, C; Meschini, S; Fabbri, A; Fiorentini, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/55911
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