TY  - JOUR
AU  - Delling, Jan Philipp
AU  - Bauer, Helen Friedericke
AU  - Gerlach-Arbeiter, Susanne
AU  - Schön, Michael
AU  - Jacob, Christian
AU  - Wagner, Jan
AU  - Pedro, Maria Teresa
AU  - Knöll, Bernd
AU  - Boeckers, Tobias M
TI  - Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
JO  - Molecular psychiatry
VL  - 29
IS  - 10
SN  - 1359-4184
CY  - London
PB  - Macmillan
M1  - DZNE-2024-00907
SP  - 2997 - 3009
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Female
KW  - Humans
KW  - Mice
KW  - Autism Spectrum Disorder: genetics
KW  - Autism Spectrum Disorder: metabolism
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Chromosome Deletion
KW  - Chromosome Disorders
KW  - Chromosomes, Human, Pair 22
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Microfilament Proteins: metabolism
KW  - Microfilament Proteins: genetics
KW  - Microscopy: methods
KW  - Nerve Tissue Proteins: metabolism
KW  - Nerve Tissue Proteins: genetics
KW  - Synapses: metabolism
KW  - Young Adult
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11449788
C6  - pmid:38649753
DO  - DOI:10.1038/s41380-024-02559-9
UR  - https://pub.dzne.de/record/270868
ER  -