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 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.

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Publication Details

Journal
EMBO Molecular Medicine
Published
2024-09-20
DOI
https://doi.org/10.1038/s44321-024-00144-9
Citations
7
Primary Topic
Genetics and Neurodevelopmental Disorders
Type
article
Field-Weighted Citation Impact
3.85

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article

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

Clara Cambria, Gianvito Martino, Flavia Antonucci, Lara Pizzamiglio et al.
7 citations
EMBO Molecular Medicine
Genetics and Neurodevelopmental Disorders
3.85
article

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

Clara Cambria, Gianvito Martino, Flavia Antonucci, Lara Pizzamiglio, Nicoletta Landsberger, Marzia Indrigo, Maria Balbontin Arenas, Ugo Borello, Francesco Bedogni, Erica Butti, Angelisa Frasca, Federica Miramondi, Arianna Piffer, Francesca M Postogna
article en
7 citations

Abstract

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.

EMBO Molecular MedicineVol. 16(12)
University of Pisa (IT), Centre National de la Recherche Scientifique (FR), Vita-Salute San Raffaele University (IT), Inserm (FR), University of Milan (IT), San Raffaele University of Rome (IT), École Normale Supérieure - PSL (FR), University Children's Hospital Zurich (CH), Institut de Biologie de l'École Normale Supérieure (FR), IRCCS Ospedale San Raffaele (IT), Cardiff University (GB)
Università degli Studi di Milano, Fondation Jérôme Lejeune, Ministero dell’Istruzione, dell’Università e della Ricerca, Banca d'Italia, Papua New Guinea University of Technology, Ministero dell'Università e della Ricerca
Good health and well-being
Openalex Percentile: Top 6%
Genetics and Neurodevelopmental Disorders
3.85
DOIOpen Access PDFOpenAlex
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