The Aged Striatum: Evidence of Molecular and Structural Changes Using a Longitudinal Multimodal Approach in Mice

Area of Science:

• Neuroscience
• Aging Research
• Medical Imaging

Background:

• Studying the aging human brain is resource-intensive.
• Mouse models offer a faster alternative to study age-related brain changes.
• Dopamine receptor availability and gray matter density are key indicators of brain health.

Purpose of the Study:

• To investigate age-related changes in dopamine D1 and D2 receptor availability in the mouse striatum.
• To assess changes in gray matter density in the aging mouse striatum.
• To evaluate the utility of longitudinal mouse imaging as a model for human brain aging.

Main Methods:

• Longitudinal structural magnetic resonance imaging (sMRI) was performed on aging mice.
• Positron emission tomography (PET) with [11C]Raclopride and [11C]SCH23390 was used to measure dopamine receptor availability.
• Voxel-based morphometry (VBM) and tensor-based morphometry (TBM) were employed for data analysis.

Main Results:

• A significant reduction in striatal dopamine D2 receptor binding potential was observed over time.
• No significant changes were detected in dopamine D1 receptor binding potential.
• sMRI revealed a significant increase in modulated gray matter density in the striatum, potentially due to non-neuronal cell proliferation.

Conclusions:

• Longitudinal PET imaging in mice can model age-related declines in striatal dopamine D2 receptors, consistent with human studies.
• The [11C]SCH23390 tracer may not yet be suitable for assessing D1 receptor changes in anesthetized mice.
• Increased gray matter density in aging mice warrants further investigation into cellular changes.