Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway.
Cytokine
Mecp2
Neurodevelopmental Disease
Stem Cells
Synapses
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: Germany
ID NLM: 101487380
Informations de publication
Date de publication:
20 Sep 2024
20 Sep 2024
Historique:
received:
07
01
2024
accepted:
04
09
2024
revised:
29
08
2024
medline:
21
9
2024
pubmed:
21
9
2024
entrez:
20
9
2024
Statut:
aheadofprint
Résumé
The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analyzed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon γ (IFNγ) pathway. Accordingly, we report the capacity of IFNγ to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT.
Identifiants
pubmed: 39304759
doi: 10.1038/s44321-024-00144-9
pii: 10.1038/s44321-024-00144-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fondation Jérôme Lejeune
ID : JLF#1951
Organisme : Ministero dell'Università e della Ricerca
ID : 2022TWKYL5
Informations de copyright
© 2024. The Author(s).
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