Stargazin mutation impairs cerebellar synaptogenesis, synaptic maturation and synaptic protein distribution

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Stargazin (stg) mutation in mice leads to absence epilepsy and cerebellar ataxia.
• Previous studies identified defects in AMPA receptor function, BDNF expression, and cerebellar cortex morphology in stg mice.

Purpose of the Study:

• To investigate the ultrastructural abnormalities of cerebellar granule cell output synapses in stg mice.
• To quantify synaptic protein expression levels in different brain regions of stg mutants.

Main Methods:

• Electron microscopy was used to examine cerebellar cortex ultrastructure.
• Quantitative measurements assessed synapse number and presynaptic terminal area.
• Immunoblotting analyzed SNARE and synapsin protein levels in synaptosomes from various brain regions.

Main Results:

• Immature synaptic features, reduced synapse number, and smaller presynaptic terminals were observed in the stg cerebellum.
• Selective reduction of synaptobrevin and synaptophysin was found in stg cerebellar synaptosomes.
• Synapsin levels were unchanged in the cerebellum but upregulated in the cerebral cortex and hippocampus of stg mice.

Conclusions:

• Stargazin mutation causes significant defects in cerebellar synaptic ultrastructure, despite normal gross cerebellar morphology.
• Regional failure of BDNF expression, linked to stargazin mutation, may contribute to abnormal SNARE protein distribution and synaptic defects.