S Gargiulo1,2, S Anzilotti3, A R D Coda1, M Gramanzini1,2, A Greco2,4, M Panico1, A Vinciguerra5, A Zannetti1, C Vicidomini1, F Dollé6, G Pignataro5, M Quarantelli1, L Annunziato3,5, A Brunetti2,4, M Salvatore3, S Pappatà7. 1. Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy. 2. Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy. 3. IRCCS SDN, Via E. Gianturco 113, 80143, Naples, Italy. 4. Department of Advanced Biomedical Sciences, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy. 5. Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy. 6. CEA, Institute for Biomedical Imaging, 4 Place du Général Leclerc, 91401, Orsay, France. 7. Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy. sabina.pappata@ibb.cnr.it.
Abstract
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.
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 SOD1mice, 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.
Authors: Da Wei Zang; Qing Yang; Hong Xin Wang; Gary Egan; Elizabeth C Lopes; Surindar S Cheema Journal: Eur J Neurosci Date: 2004-10 Impact factor: 3.386
Authors: Anna F Fusco; Angela L McCall; Justin S Dhindsa; Logan A Pucci; Laura M Strickland; Amanda F Kahn; Mai K ElMallah Journal: J Neuroinflamm Neurodegener Dis Date: 2019-11-01