Skip to Main content Skip to Navigation
Theses

Lineage-specific manipulation of subventricular zone germinal activity for neonatal cortical repair

Abstract : Perinatal hypoxia leads to degeneration and delayed maturation of oligodendrocytes and cortical glutamatergic neurons. My PhD project consists in assessing the contribution of neural stem cells (NSCs) of the dorsal subventricular zone (dSVZ, i.e. the largest germinal zone of the postnatal brain) to the spontaneous regenerative attempt observed following such injury as well as its amenability to pharmacological manipulation.The results I have obtained highlight a dynamic and lineage-specific response of NSCs of the dSVZ to hypoxia that results in de novo oligodendrogenesis and cortical neurogenesis. Newborn cortical neurons express appropriate cortical layer markers, supporting their appropriate specification. A pharmacogenomics analysis allowed us to identify small molecules boosting specificly dSVZ NSCs. Pharmacological activation of Wnt/ß-catenin signalling by intranasal GSK3ß inhibitor administration during the recovery period following hypoxia indeed potentiates dorsal SVZ participation to post-hypoxia repair. Gsk3b inhibitor CHIR99021 seems to promote survival of cortical neurons from the dSVZ produced in response to hypoxia. More interestingly, CHIR99021 promotes oligodendrocyte maturation and long term integration in the cortex as well as a long term increased activity of dSVZ NSCs.Altogether, my results highlighted a dynamic and lineage-specific response of dorsal NSCs cells to hypoxia and identify the early postnatal dorsal SVZ as a malleable source of stem cells for cortical repair following trauma that occur early in life. CHIR99021 (a Gsk3b inhibitor) intranasal administration promotes this cortical cellular repair with a long term activation of dSVZ NSCs which increased their production of oligodendrocytes migrating to the cortex and a short term improvement of their maturation, and might allow the integration of cortical neurons they produce
Document type :
Theses
Complete list of metadatas

Cited literature [486 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01827013
Contributor : Abes Star :  Contact
Submitted on : Sunday, July 1, 2018 - 1:02:39 AM
Last modification on : Thursday, October 29, 2020 - 3:33:22 AM
Long-term archiving on: : Monday, October 1, 2018 - 2:53:54 AM

File

TH2017AngoninDiane.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01827013, version 1

Collections

Citation

Diane Angonin. Lineage-specific manipulation of subventricular zone germinal activity for neonatal cortical repair. Neuroscience. Université de Lyon, 2017. English. ⟨NNT : 2017LYSE1175⟩. ⟨tel-01827013⟩

Share

Metrics

Record views

165

Files downloads

199