Journal Article

DZNE-2024-00907

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.

Delling, J. P. ; Bauer, H. F. ; Gerlach-Arbeiter, S. ; Schön, M. ; Jacob, C. ; Wagner, J. ; Pedro, M. T. ; Knöll, B. ; Boeckers, T. M. (Last author)DZNE*

2024
Macmillan London

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Please use a persistent id in citations: doi:10.1038/s41380-024-02559-9

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.

Keyword(s): Animals (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Autism Spectrum Disorder: genetics (MeSH) ; Autism Spectrum Disorder: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Brain: pathology (MeSH) ; Chromosome Deletion (MeSH) ; Chromosome Disorders (MeSH) ; Chromosomes, Human, Pair 22 (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Microfilament Proteins: metabolism (MeSH) ; Microfilament Proteins: genetics (MeSH) ; Microscopy: methods (MeSH) ; Nerve Tissue Proteins: metabolism (MeSH) ; Nerve Tissue Proteins: genetics (MeSH) ; Synapses: metabolism (MeSH) ; Young Adult (MeSH)

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Contributing Institute(s):

1. Translational Protein Biochemistry (AG Böckers)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Delling, J. P. ; Bauer, H. F. ; Gerlach-Arbeiter, S. ; Schön, M. ; Jacob, C. ; Wagner, J. ; Pedro, M. T. ; Knöll, B. ; Böckers, T. (Last author)DZNE*
Dataset: Data, code, and images underlying figures in the manuscript 'Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency'
Edmond (2024) [10.17617/3.UYFDS3]2024   Files BibTeX | EndNote: XML, Text | RIS

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