Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway

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 fir...

Full description

Saved in:

Bibliographic Details
Published in:	EMBO molecular medicine
Main Authors:	Frasca, Angelisa, Miramondi, Federica, Butti, Erica, Indrigo, Marzia, Balbontin Arenas, Maria, Postogna, Francesca M, Piffer, Arianna, Bedogni, Francesco, Pizzamiglio, Lara, Cambria, Clara, Borello, Ugo, Antonucci, Flavia, Martino, Gianvito, Landsberger, Nicoletta
Format:	Journal Article
Language:	English
Published:	Germany 20-09-2024
Subjects:	Stem Cells Mecp2 Neurodevelopmental Disease Synapses Cytokine
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1757-4684 1757-4684
DOI:	10.1038/s44321-024-00144-9