Dans cette étude, nous avons utilisé un modèle de souris permettant d’induire des lésions de sévérité variable afin de mimer différentes anomalies de la myéline du cerveau que l'on peut rencontrer chez l'homme. La perte des OLs a été de 80% après 2 semaines de traitement au GCV (GCV1-14). Après l'arrêt du traitement, les processus de récupération ont conduit à une augmentation significative de la population OLs à 80% à la semaine 6 (W6). L’extension du traitement GCV à 3 semaines (GCV1-21) a entraîné une perte de 85% de la population OLs. Cependant la récupération est limitée et reste à 40% du niveau de contrôle à W6. Nous avons remarqué une augmentation rapide (de 2 fois) des cellules Olig2+ chez la souris GCV1-14 contre les souris GCV1-21 (de 1,5 fois) à W4. Nos résultats ont montré une augmentation significative des cellules Olig2-phosphorylé chez la souris GCV1-14 entre W3 et W4 après l'arrêt du traitement GCV. A l'opposé, dans le modèle GCV1-21, un très faible niveau de Olig2 phosphorylé a été observé. Nous avons observé des modifications transitoires dans l’expression de NgR et Caspr mais l’expression de P75 reste inchangée. Ensemble, ces résultats suggèrent que la reprise du déficit myéline du cerveau au cours du développement postnatal dépend de régénération suffisante des oligodendrocytes dans un laps de temps défini pour la myélinisation normale. / Abnormalities of myelination during brain development are thought to result in neurologic and psychiatric disorders. We tested the developmental time window required for oligodendrocyte generation and myelin formation in the central nervous system, using a transgenic mouse harboring HSV1-TK and eGFP genes under the control of MBP and PLP promoters respectively, to carry out the conditional ablation of oligodendrocytes. The first ablation program comprised daily injection of ganciclovir (GCV) for two weeks (GCV1-14) to induce a reversible myelin recovery. The second program comprised GCV injection for 3 weeks (GCV1-21) to create a model of irreversible myelin recovery. GCV1-14 model presented 85% reduction of oligodendrocytes at week 2 (W2) and significantly increased recovery of oligodendrocytes and myelin at W4, then slower recuperation in the following weeks after the arrest of GCV treatment. Similarly, GCV treatment for three weeks (GCV1-21) induced severe deficiency of oligodrndocytes (90%) and myelin at W3. Contrasting the GCV1-14 program, only 40-50% of oligodendrocyte population was recovered at W6 and brain remained severely deficient in myelin. Moreover, no significant recovery was observed during the following weeks and myelin at W4, then slower recuperation in the following weeks after the arrest of GCV treatment. Similarly, GCV treatment for three weeks (GCV1-21) induced severe deficiency of oligodrndocytes (90%) and myelin at W3. Contrasting the GCV1-14 program, only 40-50% of oligodendrocyte population was recovered at W6 and brain remained severely deficient in myelin. Moreover, no significant recovery was observed during the following weeks and frequently ended with premature death of mice. Since no significant changes in the expression of axonal markers including neurofilaments, NgR, P75, Caspr and neurofascin186 were detected at W5 in the two models, we conclude that an intrinsic defect of oligodendrocyte regeneration at W3-W4 underlies the irreversible model. Significant number of phosphorylated Olig2+ cells was observed at W3 in reversible model in demyelinated corpus callosum while at the same time-point, this population is absent from control and irreversible model. At the same period, the proliferation index (Ki67) of Olig2+ cells is 8 fold higher in the corpus callosum of GCV1-14 model than the control and the irreversible model. Together, these findings suggest that recovery from myelin deficit during postnatal brain development depends on sufficient regeneration of oligodendrocytes within a defined time frame for normal myelination to occur.