Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
Jan Philipp DellingHelen Friedericke BauerSusanne Gerlach-ArbeiterMichael SchönChristian JacobJan WagnerMaria Teresa PedroBernd KnöllTobias M BöckersPublished in: Molecular psychiatry (2024)
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.
Keyphrases
- high resolution
- autism spectrum disorder
- prefrontal cortex
- single molecule
- resting state
- white matter
- endothelial cells
- high speed
- attention deficit hyperactivity disorder
- healthcare
- bipolar disorder
- optical coherence tomography
- high throughput
- functional connectivity
- intellectual disability
- multiple sclerosis
- cerebral ischemia
- type diabetes
- adipose tissue
- metabolic syndrome
- insulin resistance
- skeletal muscle
- brain injury
- case report
- working memory
- single cell
- pluripotent stem cells