Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B.
Administration, Intranasal
Animals
Autistic Disorder
/ genetics
Behavior, Animal
Blood-Brain Barrier
/ pathology
Brain
/ pathology
Disease Models, Animal
Exosomes
/ metabolism
Male
Mesenchymal Stem Cells
/ metabolism
Mice, Knockout
Microfilament Proteins
/ genetics
Nerve Tissue Proteins
/ genetics
Phenotype
Social Behavior
gamma-Aminobutyric Acid
/ metabolism
Journal
Molecular autism
ISSN: 2040-2392
Titre abrégé: Mol Autism
Pays: England
ID NLM: 101534222
Informations de publication
Date de publication:
17 08 2020
17 08 2020
Historique:
received:
08
03
2020
accepted:
22
07
2020
entrez:
19
8
2020
pubmed:
19
8
2020
medline:
4
8
2021
Statut:
epublish
Résumé
Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan-McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect. Exosomes derived from MSC (MSC-exo) were purified, characterized, and given via intranasal administration to Shank3B KO mice (in the concentration of 10 Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization, and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex. Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mouse model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model of autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.
Sections du résumé
BACKGROUND
Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan-McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect.
METHODS
Exosomes derived from MSC (MSC-exo) were purified, characterized, and given via intranasal administration to Shank3B KO mice (in the concentration of 10
RESULTS
Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization, and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex.
CONCLUSIONS
Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mouse model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model of autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.
Identifiants
pubmed: 32807217
doi: 10.1186/s13229-020-00366-x
pii: 10.1186/s13229-020-00366-x
pmc: PMC7433169
doi:
Substances chimiques
Microfilament Proteins
0
Nerve Tissue Proteins
0
Shank3 protein, mouse
0
gamma-Aminobutyric Acid
56-12-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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