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Effets de l’administration chronique de corticostérone sur le développement postnatal du cervelet

Abstract : During the prenatal period, the cerebellum is immature and particularly vulnerable to stressors such as repetitive maternal deprivation or supra-physiological glucocorticoid exposure that might impact the normal cerebellar development and its functions. However, the potentials effects of glucocorticoids during the postnatal developmental window from postnatal day 8 (PND8) to PND29 that corresponds to 1) the set-up of climbing fiber innervation on the dendritic arborization of Purkinje cells, 2) granule cell proliferation and migration and 3) Purkinje cell – parallel fibers synaptogenesis, are not well established. So the purpose of the present study was to determine whether 1) chronic corticosterone treatment during this period could affect the development and the maturation of the cerebellum; 2) glucocorticoids could change the expression of genes encoding for several factors involved in the different steps of the cerebellar development; and 3) chronic corticosterone administered during the postnatal period could have long-term effects on cerebellar functions. In the present study, mice were injected with corticosterone (20 mg/kg) or dimethylsulfoxyde (control group) from PND8 to PND29. Results show that chronic corticosterone delivered from PND 8 to 29 affect the cerebellar and hippocampal development: morphological changes and downregulation or upregulation of gene encoding for neurotrophic factor, corticotropin releasing hormone (CRH), were observed at PND 15 and 29. Furthermore, changes in morphological, regional metabolic activity, gene expression, and sensori-motor phenotype were also highlighted at adult period, illustrating the long-term impact of early corticosterone administration on cerebellar development. Finally, chronic corticosterone injection during the postnatal period modified the stress response at adulthood as shown by the stress hormones assays performed in the hypothalamus and hippocampus. This study illustrates the long-effect impact of early in life corticosterone administration on the structure of the cerebellum and cerebellar-mediated functions.
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Magali Hernandez. Effets de l’administration chronique de corticostérone sur le développement postnatal du cervelet. Biologie du développement. Université de Lorraine, 2019. Français. ⟨NNT : 2019LORR0304⟩. ⟨tel-02860510⟩

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