Reduced brain volume and white matter alterations in Shank3-deficient rats

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Mutations in the SHANK3 gene are linked to Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder.
• SHANK3 is crucial for excitatory synapse structure and function, impacting synaptogenesis.

Purpose of the Study:

• To assess in vivo brain structure in adult Shank3-deficient rats.
• To investigate if Shank3 deficiency replicates PMS-associated brain alterations.

Main Methods:

• Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were used on adult Shank3-deficient and wild-type rats.
• Anatomical and white matter tract integrity were analyzed.

Main Results:

• Shank3-deficient rats displayed reduced overall brain volume, including neocortex, thalamus, and superior colliculus.
• DTI revealed abnormalities in white matter tracts like the external capsule and fornix, indicating impaired axonal integrity.

Conclusions:

• Shank3-deficient rats serve as a valid model for PMS, replicating key brain structural deficits.
• Altered brain regions in Shank3-deficient rats may represent cross-species biomarkers for PMS research.