Motor learning deficits and striatal GSK-3 hyperactivity in Akt3 knockout mice.
Behav Neurosci
; 133(1): 135-143, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30688489
ABSTRACT
Akt protein family (Akt1, Akt2 and Akt3) of serine/threonine kinases, also known as protein kinase B, are enzymes implicated in many physiological and pathological processes in the central nervous system. A striking feature of these enzymes is their ability to interact with several molecular targets such as the glycogen synthase kinase 3 (GSK-3). Among Akt isoforms, the Akt3 is significantly more expressed in the brain and the present investigation was designed to determine whether the Akt3/GSK-3 pathway plays a role in the learning of a complex motor skill. Using the accelerating rotarod task, known to reproduce different motor learning phases, we demonstrated in mouse models that genetic deletion of GSK-3α or GSK-3ß had no effect on rotarod performances. However, Akt3 deletion robustly compromised rotarod learning when compared with wild-type animals. Biochemical analysis in the striatum revealed modifications in the levels of both phosphorylated GSK-3 and tau in Akt3-deficient mice, which are reminiscent of enhanced GSK-3 activity. In this line, we observed that both biochemical and motor learning impairments were prevented in Akt3-deficent mice by chronic treatments with lithium, a well-known GSK-3 inhibitor. Altogether, our findings raised the interesting possibility that interconnection between Akt3 and GSK-3 kinases is required in the learning of new complex motor tasks. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Corpo Estriado
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Quinase 3 da Glicogênio Sintase
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Glicogênio Sintase Quinase 3 beta
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Aprendizagem
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Destreza Motora
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article