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Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency
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Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency
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Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency
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Journal Article
Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency
2024
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/51
/ 14/63
/ 631/378
/ 64/60
/ Animals
/ Autism
/ Autism Spectrum Disorder - genetics
/ Autism Spectrum Disorder - metabolism
/ Brain
/ Female
/ Humans
/ Male
/ Medicine
/ Mice
/ Microfilament Proteins - genetics
/ Microfilament Proteins - metabolism
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Tissues
