AI Article Synopsis
- - Synaptic dysfunction plays a crucial role in SHANK-associated disorders like autism, schizophrenia, and Phelan-McDermid syndrome, but understanding its effects on synaptic structure is limited.
- - The study used advanced imaging techniques (expansion and STED microscopy) to examine the synaptic nanostructures in both human and mouse brain tissues, focusing on SHANK3-KO mice.
- - Findings revealed unique shape profiles of murine postsynaptic scaffolds and significant changes in the organization of synaptic domains due to SHANK3 deficiency, shedding light on the molecular mechanisms of synaptic dysfunction in neuropsychiatric disorders.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449788 | PMC |
| http://dx.doi.org/10.1038/s41380-024-02559-9 | DOI Listing |
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