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 an 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 analysed 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

Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway / A. Frasca, F. Miramondi, E. Butti, M. Indrigo, M. BALBONTIN ARENAS, F.M. Postogna, A. Piffer, F. Bedogni, L. Pizzamiglio, C. Cambria, U. Borello, F. Antonucci, G. Martino, N. Landsberger. - (2024 Jan 08). [10.1101/2024.01.07.574507]

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

A. Frasca
Co-primo
;
F. Miramondi
Co-primo
;
M. BALBONTIN ARENAS;F.M. Postogna;L. Pizzamiglio;C. Cambria;F. Antonucci;N. Landsberger
Ultimo
2024

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 an 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 analysed 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
No
English
cytokine; Mecp2; neurodevelopmental disease; stem cells; synapses;
Settore BIO/11 - Biologia Molecolare
8-gen-2024
41
https://www.biorxiv.org/content/10.1101/2024.01.07.574507v1
Aderisco
298
14
Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway / A. Frasca, F. Miramondi, E. Butti, M. Indrigo, M. BALBONTIN ARENAS, F.M. Postogna, A. Piffer, F. Bedogni, L. Pizzamiglio, C. Cambria, U. Borello, F. Antonucci, G. Martino, N. Landsberger. - (2024 Jan 08). [10.1101/2024.01.07.574507]
Prodotti della ricerca::24 - Pre-print
A. Frasca, F. Miramondi, E. Butti, M. Indrigo, M. BALBONTIN ARENAS, F.M. Postogna, A. Piffer, F. Bedogni, L. Pizzamiglio, C. Cambria, U. Borello, F. A...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1041912
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