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Synaptic density in aging mice measured by [18F]SynVesT-1 PET
Mengfei Xiong1, Sahar Roshanbin1, Dag Sehlin1
1Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
Neuroimage
|June 24, 2023
Summary
Positron emission tomography (PET) with [18F]SynVesT-1 reveals decreased synaptic density in older mice. This study explores synaptic changes during aging using SV2A PET imaging in healthy mice.
Area of Science:
- Neuroscience
- Radiochemistry
- Gerontology
Background:
- Synaptic alterations correlate with cognitive decline in aging and neurodegeneration.
- Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) visualizes synaptic loss in neurodegenerative diseases.
- SV2A PET's utility in studying aging-related synaptic changes remains underexplored.
Purpose of the Study:
- To investigate age-related synaptic density changes in healthy mice using PET imaging.
- To evaluate the PET ligand [18F]SynVesT-1 for assessing synaptic vesicle glycoprotein 2A (SV2A) binding in aging.
Main Methods:
- Healthy C57BL/6 mice (4-5, 12-14, 17-19 months) underwent PET scans with [18F]SynVesT-1.
- Brain retention (V_IDIF) was calculated using an image-derived input function and analyzed with one-tissue compartment model (1TCM).
- Post-PET, immunostaining assessed SV2A expression and neuronal markers.
Main Results:
- [18F]SynVesT-1 demonstrated suitable brain pharmacokinetics in mice when analyzed with 1TCM.
- The oldest mice group exhibited lower [18F]SynVesT-1 retention, suggesting reduced synaptic density.
- Immunostaining revealed consistent SV2A expression and neuron numbers across age groups.
Conclusions:
- [18F]SynVesT-1 PET imaging can effectively assess synaptic density changes during aging in mice.
- A decrease in synaptic density was observed in the oldest mice, aligning with human aging studies.
- No region-specific, gradual age-dependent decline in synaptic density was detected in this healthy aging mouse model.
