Étude de l’apprentissage d’une tâche motrice : implication de la voie Akt-GSK-3
The production of the human's movements, and among many other animals, can be effortlessly executed during the realization of a complex motor task. These highly coordinated movements require the integration of several orders coming from different regions of the brain, notably the motor areas of the cerebral cortex, basal ganglia and the cerebellum. Despite the recent progress in neuroscience, motor learning mechanism is still not completely understood. The way that the brain integrates and memorizes the motor movements during a motor activity is still not completely known. The protein kinase B (PKB/Akt) is a serine/threonine kinase highly conserved among the mammals and control several cellular metabolisms such as the proliferation, the survival and the cellular plasticity. Akt has three isoforms (Akt1, Akt2 and Akt3) that are encoded by three distinct genes. It is important to note that Akt3 is more expressed in the brain than Akt1 and Akt2. Glycogen Synthase Kinase-3 (GSK-3) includes two isoforms, GSK-3alpha and GSK-3beta. Akt and the protein kinase GSK-3 are closely connected. Certainly, it is well established that Akt reduces the activity of GSK-3 alpha/beta by its phosphorylation on the serine 21/9 respectively. A disruption of the Akt/GSK-3 pathway has been linked to several pathologies such as depression, schizophrenia and the bipolar disorder. The mainstream of my research was to study the capacity of training, performance and memorization of a complex motor task among mice having a genetic Akt3 deletion (Akt3 KO). The results on the rotarod demonstrated that Akt3 deletion compromised rotarod performances in comparison to wild type mice (WT). Interestingly, my results demonstrated a change of the phosphorylation of GSK-3 alpha/beta and propose that the motor training deficit would be caused by GSK-3 alpha/beta hyperactivation, induced by the genetic deletion of Akt3. It is interesting to note that lithium chronic treatment, which is known to inhibit directly and indirectly the GSK-3 protein, corrected the training deficit of Akt3 KO mice. Our results have established an important implication of the Akt3/GSK -3 pathway in motor training.
Akt3 GSK-3 Rotarod Striatum Lithium Motor learning