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Titolo:
Inducible, pharmacogenetic approaches to the study of learning and memory
Autore:
Ohno, M; Frankland, PW; Chen, AP; Costa, RM; Silva, AJ;
Indirizzi:
Univ Calif Los Angeles, Brain Res Inst, Dept Neurobiol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Brain Res Inst, Dept Psychiat, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Brain Res Inst, Dept Psychol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA
Titolo Testata:
NATURE NEUROSCIENCE
fascicolo: 12, volume: 4, anno: 2001,
pagine: 1238 - 1243
SICI:
1097-6256(200112)4:12<1238:IPATTS>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-II; LONG-TERM POTENTIATION; MAP KINASE; CONTEXTUAL FEAR; MOUSE GENOME; RAS; HIPPOCAMPUS; ACTIVATION; CASCADE; PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Silva, AJ Univ Calif Los Angeles, Brain Res Inst, Dept Neurobiol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 s, CA 90095 USA
Citazione:
M. Ohno et al., "Inducible, pharmacogenetic approaches to the study of learning and memory", NAT NEUROSC, 4(12), 2001, pp. 1238-1243

Abstract

Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K-ras gene (K-ras(+/-)) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls,blocks MAPK activation, LTP and contextual learning in K-ras(+/-) mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the alpha CaMKII gene, but not in K-ras(+/-) mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-ras(+/-) mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 22:42:15