Brain metabolic and behavioral alterations in a Down syndrome model

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Down syndrome is associated with cognitive deficits and increased risk of neurodegeneration.
• The Ts65Dn mouse is a widely used model for Down syndrome, exhibiting some trisomic features.
• Longitudinal studies are crucial for understanding age-dependent changes in disease models.

Purpose of the Study:

• To longitudinally monitor the Ts65Dn mouse model of Down syndrome across its lifespan.
• To detect time-dependent in vivo molecular alterations related to neurodegeneration and neuroinflammation.
• To correlate neuroimaging findings with behavioral and post-mortem analyses.

Main Methods:

• Longitudinal [18F]FDG PET imaging and behavioral tasks in euploid and Ts65Dn mice at 2, 5, 14, 20, and 24 months.
• Analysis of brain metabolism using VOI-based SUV, voxel-wise, and metabolic network approaches.
• Post-mortem brain analysis for neuronal loss (NeuN) and microglia activation (Iba-1).

Main Results:

• Brain metabolism increased at 14 months in both genotypes.
• [18F]FDG uptake correlated with microglia activation, indicating neuroinflammation.
• Older trisomic mice showed greater metabolic network desynchronization and impaired memory recognition at 24 months.

Conclusions:

• This is the first lifelong [18F]FDG PET study of the Ts65Dn mouse model.
• Trisomic mice exhibit early disruption in brain network organization.
• These disruptions likely contribute to aging, neurodegeneration, and neuroinflammation-related functional impairments.