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- W4236137534 abstract "Abstract Background : Mutations and deletions in the SHANK3 synaptic gene cause the major neurodevelopmental features of Phelan-McDermid syndrome (PMS). The SHANK3 gene encodes a key structural component of excitatory synapses that is important for synaptogenesis. PMS is characterized by intellectual disability, autism spectrum disorder, cognitive deficits, physical dysmorphic features, sensory hyporeactivity, and alterations in the size of multiple brain regions. Clinical assessments and limited imaging studies have revealed a reduction in volume of multiple brain regions. They have also found white matter thinning and microstructural alterations to be persistent in patients with PMS. While many of these impairments have been replicated in mouse models of PMS, the brain structure of a rat model has not yet been studied. Methods : We assessed the brain structure of haploinsufficient and homozygous Shank3 -deficient rats that model the behavioral deficits of PMS with magnetic resonance and diffusion tensor imaging, and compared their brain structure to wild type littermates. Results : Both gray and white matter structures were smaller in Shank3 -deficient rats, leading to an overall reduction in brain size compared to wild type littermates. The largest region to be diminished in size was the neocortex. Some regions involved in sensory processing and white matter regions were also reduced in size. Lastly, the microstructure of two white matter tracts, the external capsule and fornix, was abnormal. Conclusions : Shank3-deficient rats replicate the reduced brain volume and altered white matter phenotypes present in individuals with PMS. Therefore, the brain regions that were altered represent potential cross-species structural biomarkers that warrant further study." @default.
- W4236137534 created "2022-05-12" @default.
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- W4236137534 date "2020-11-04" @default.
- W4236137534 modified "2023-09-28" @default.
- W4236137534 title "Reduced Brain Volume and White Matter Alterations in Shank3-Deficient Rats" @default.
- W4236137534 doi "https://doi.org/10.21203/rs.3.rs-100329/v1" @default.
- W4236137534 hasPublicationYear "2020" @default.
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