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Published on: June 14, 2018
Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with (18)F-DPA-714 and
S Gargiulo1,2, S Anzilotti3, A R D Coda1
1Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
Purpose:
To evaluate the feasibility and sensitivity of (18)F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1(G93A) mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry.
Methods:
Nine symptomatic SOD1(G93A) mice (aged 117 ± 12.7 days, clinical score range 1 - 4) and five WT SOD1 control mice (aged 108 ± 28.5 days) underwent (18)F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebellar (rCRB), brainstem (rBS), motor cortex (rMCX) and cervical spinal cord (rCSC) activities to that of the frontal association cortex. Two WT SOD1 and six symptomatic SOD1(G93A) mice were studied by immunohistochemistry.
Results:
In the symptomatic SOD1(G93A) mice, rCRB, rBS and rCSC were increased as compared to the values in WT SOD1 mice, with a statistically significantly difference in rBS (2.340 ± 0.784 vs 1.576 ± 0.287, p = 0.014). Immunofluorescence studies showed that TSPO expression was increased in the trigeminal, facial, ambiguus and hypoglossal nuclei, as well as in the spinal cord, of symptomatic SOD1(G93A) mice and was colocalized with increased Iba1 staining.
Conclusion:
Increased (18)F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1(G93A) mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, (18)F-DPA-714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1(G93A) mouse model.
Insights
Positron emission tomography (PET) with (18)F-DPA-714 can detect microglial activation in the brainstem of SOD1(G93A) mice. This imaging technique shows promise for studying neuroinflammation in mouse models of amyotrophic lateral sclerosis.
Area of Science:
- Neuroscience
- Molecular Imaging
- Biochemistry
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Microglial activation is a key pathological feature in ALS.
- Transgenic SOD1(G93A) mice are a widely used model for studying ALS.
Purpose of the Study:
- To assess the feasibility and sensitivity of (18)F-DPA-714 for imaging microglial activation in the brain and spinal cord of SOD1(G93A) mice.
- To correlate PET findings with immunohistochemical markers of microglial activation (Iba1 and TSPO).
Main Methods:
- High-resolution PET/CT imaging with (18)F-DPA-714 was performed on symptomatic SOD1(G93A) mice and wild-type (WT) SOD1 controls.
- Standardized uptake value (SUV) ratios were calculated for various brain regions and the spinal cord.
- Immunohistochemistry was used to evaluate Iba1 and TSPO expression.
Main Results:
- Increased (18)F-DPA-714 uptake was observed in the brainstem (rBS) of symptomatic SOD1(G93A) mice compared to WT controls (p=0.014).
- Immunofluorescence confirmed increased TSPO expression, co-localized with Iba1 staining, in the brainstem nuclei and spinal cord of SOD1(G93A) mice.
Conclusions:
- High-resolution PET/CT with (18)F-DPA-714 can detect increased microglial activation in the brainstem of SOD1(G93A) mice.
- This finding aligns with increased TSPO expression, suggesting (18)F-DPA-714 PET/CT is a viable tool for studying neuroinflammation in this ALS mouse model.
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