%0 Journal Article
%A Delling, Jan Philipp
%A Bauer, Helen Friedericke
%A Gerlach-Arbeiter, Susanne
%A Schön, Michael
%A Jacob, Christian
%A Wagner, Jan
%A Pedro, Maria Teresa
%A Knöll, Bernd
%A Boeckers, Tobias M
%T Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
%J Molecular psychiatry
%V 29
%N 10
%@ 1359-4184
%C London
%I Macmillan
%M DZNE-2024-00907
%P 2997 - 3009
%D 2024
%X 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.
%K Animals
%K Female
%K Humans
%K Mice
%K Autism Spectrum Disorder: genetics
%K Autism Spectrum Disorder: metabolism
%K Brain: metabolism
%K Brain: pathology
%K Chromosome Deletion
%K Chromosome Disorders
%K Chromosomes, Human, Pair 22
%K Mice, Inbred C57BL
%K Mice, Knockout
%K Microfilament Proteins: metabolism
%K Microfilament Proteins: genetics
%K Microscopy: methods
%K Nerve Tissue Proteins: metabolism
%K Nerve Tissue Proteins: genetics
%K Synapses: metabolism
%K Young Adult
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC11449788
%$ pmid:38649753
%R 10.1038/s41380-024-02559-9
%U https://pub.dzne.de/record/270868