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Synaptic degeneration in the prefrontal cortex of a rat AD model revealed by volume electron microscopy

Summary

Researchers used advanced microscopy techniques to examine brain tissue from rats with Alzheimer’s disease and compared it to healthy rats. They found that Alzheimer’s disease causes damage to connections between brain cells (synapses) in a brain region important for thinking and memory. Specifically, the connections were weaker and smaller, and many new spine-like structures formed but didn’t properly connect to other cells, suggesting the brain may be trying unsuccessfully to compensate for the disease.

Background

Alzheimer’s disease (AD) is the most common cause of dementia with synaptic degeneration believed to underlie progressive cognitive decline. The prefrontal cortex plays a crucial role in executive function and is vulnerable to neurodegeneration in AD. While synaptic dysfunction is key to AD pathophysiology, specific ultrastructural changes in synapses remain poorly characterized due to lack of quantitative tools.

Objective

To perform detailed 3D ultrastructural analysis of synapses and dendrites in layer 4 of the prefrontal cortex between AD and wild-type rats using volume electron microscopy and artificial intelligence-assisted reconstruction.

Results

AD rats showed significant reductions in synaptic density (0.478 vs 0.549 synapses/μm³), synaptic apposition surface, and postsynaptic density volume compared to wild-type controls. Despite an increase in total dendritic spine number in AD rats, many thin spines lacked synapses and were not involved in synaptic transmission. More inhibitory synapses formed on dendritic shafts in AD rats.

Conclusion

Volume EM combined with deep-learning tools revealed significant ultrastructural synaptic deficits in the AD rat model at the nanoscale level, including decreased synaptic numbers, reduced contact areas, and altered spine morphology. This methodology provides a quantitative approach for studying synaptic pathology in animal models of Alzheimer’s disease.
  • Published in:Journal of Molecular Cell Biology,
  • Study Type:Research Study,
  • Source: PMID: 35238943, DOI: 10.1093/jmcb/mjac012
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