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Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
- Source :
-
Molecular psychiatry [Mol Psychiatry] 2024 Oct; Vol. 29 (10), pp. 2997-3009. Date of Electronic Publication: 2024 Apr 22. - Publication Year :
- 2024
-
Abstract
- Synaptic dysfunction is a key feature of SHANK-associated disorders such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we aimed to investigate such alterations in ex11|SH3 SHANK3-KO mice combining expansion and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins in both human and murine brain tissue. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molecular organization of subsynaptic domains under SHANK3-deficient conditions. These results provide insights into synaptic nanostructure in situ and advance our understanding of molecular mechanisms underlying synaptic dysfunction in neuropsychiatric disorders.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Humans
Mice
Chromosome Deletion
Chromosome Disorders
Chromosomes, Human, Pair 22
Mice, Inbred C57BL
Microfilament Proteins metabolism
Microfilament Proteins genetics
Microscopy methods
Young Adult
Autism Spectrum Disorder genetics
Autism Spectrum Disorder metabolism
Brain metabolism
Brain pathology
Mice, Knockout
Nerve Tissue Proteins metabolism
Nerve Tissue Proteins genetics
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5578
- Volume :
- 29
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 38649753
- Full Text :
- https://doi.org/10.1038/s41380-024-02559-9