Shankopathies in the Developing Brain in Autism Spectrum Disorders.

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Developmental Disorders

Background:

• SHANK proteins are crucial for the postsynaptic density in excitatory synapses.
• Mutations in SHANK genes are strongly associated with autism spectrum disorder (ASD).
• ASD involves behavioral changes like repetitive behaviors, social deficits, and impaired learning.

Purpose of the Study:

• To investigate synaptic function and plasticity in rodent models of Shank-related ASD.
• To explore how SHANK deficiencies impact brain wiring during development and onward.
• To identify affected brain regions and synaptic phenotypes in Shankopathies.

Main Methods:

• Analysis of rodent models with SHANK mutations.
• Examination of synaptic function and plasticity across different brain regions.
• Assessment of NMDA receptor function and excitation-inhibition balance.

Main Results:

• SHANK mutations lead to altered synaptic function, including weakened or strengthened transmission.
• NMDA receptor function and excitation-inhibition balance are commonly affected.
• Deficits in brain regions like the striatum, hippocampus, and cortex, as well as hypothalamus and cerebellum, were observed.

Conclusions:

• Developmental SHANK deficiencies can cause permanent alterations in brain circuitry.
• Understanding these synaptic changes is key for developing therapeutic interventions for shankopathies.
• Further research is needed to address remaining questions and challenges in the field.