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@article{rodriguez-duboc2023,
author = {Rodriguez-Duboc, Agalic and Basille-Duguay, Magali and
Debonne, Aurélien and Rivière, Marc-Aurèle and Vaudry, David and
Burel, Delphine},
title = {Apnea of {Prematurity} Induces Short and Long-Term
Development-Related Transcriptional Changes in the Murine
Cerebellum},
journal = {Current Research in Neurobiology},
volume = {5},
pages = {100113},
date = {2023-10-20},
url = {https://www.sciencedirect.com/science/article/pii/S2665945X23000414},
doi = {10.1016/j.crneur.2023.100113},
issn = {2665-945X},
langid = {en},
abstract = {Apnea of prematurity (AOP) occurs in over 50\% of preterm
infants and induces a perinatal intermittent hypoxia (IH) which
represents a leading cause of morbimortality worldwide. At birth,
the human cerebellar cortex is still immature, making it vulnerable
to perinatal events. Moreover, a correlation between cerebellar
functions and the deficits observed in children having suffered from
AOP has been demonstrated. Yet, the cerebellar alterations
underpinning this link remain poorly understood. To shed light on
the involvement of the cerebellum in perinatal hypoxia-related
sequelae, we developed a mouse model of AOP. In previous works, we
found that IH induces oxidative stress in the developing cerebellum
as shown by the overexpression of genes involved in reactive oxygen
species production, and the under-expression of genes encoding
antioxidant enzymes. These alterations suggest a failure of the
defense system against oxidative stress and could be responsible for
neuronal death in the cerebellum. Based on these results, we
performed a transcriptomic study of the genes involved in the
processes that occur during cerebellar development. We analyzed the
expression of these genes at various developmental stages and in
different cell types, by real time PCR. This enabled us to pinpoint
a timeframe of vulnerability at P8, which represents the age with
the highest number of downregulated genes in the cerebellum.
Moreover, we identified several molecular pathways that are impacted
by our IH protocol, such as proliferation, migration, and
differentiation. This suggests that IH can modify the development of
various cells, and then contribute to the histological and
behavioral deficits already observed in this model. Overall, our
data indicate that the cerebellum is highly sensitive to IH, and
provide elements to better understand the pathophysiology of AOP by
deciphering its cellular and molecular causal mechanisms. In the
long term, the present results could lead to the identification of
novel therapeutic targets to improve the clinical management of this
highly prevalent pathology.}
}
For attribution, please cite this work as:
Rodriguez-Duboc, A., Basille-Duguay, M., Debonne, A., Rivière, M.-A.,
Vaudry, D., & Burel, D. (2023). Apnea of Prematurity induces short
and long-term development-related transcriptional changes in the murine
cerebellum. Current Research in Neurobiology, 5,
100113. https://doi.org/10.1016/j.crneur.2023.100113