Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study
Abstract The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson’s disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical...
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-55233-z |
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| author | Tatsuhiro Terada Tomoyasu Bunai Takanori Hashizume Takashi Matsudaira Masamichi Yokokura Hirotsugu Takashima Takashi Konishi Tomokazu Obi Yasuomi Ouchi |
| author_facet | Tatsuhiro Terada Tomoyasu Bunai Takanori Hashizume Takashi Matsudaira Masamichi Yokokura Hirotsugu Takashima Takashi Konishi Tomokazu Obi Yasuomi Ouchi |
| author_sort | Tatsuhiro Terada |
| collection | DOAJ |
| description | Abstract The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson’s disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1–2), and age-matched normal subjects. PD patients were randomly divided into two groups: one (zonisamide+) that did and one (zonisamide−) that did not undergo zonisamide therapy. Annual changes in neuroinflammation ([11C]DPA713 PET), dopamine transporter availability ([11C]CFT PET) and clinical severity were examined. Voxelwise differentiations in the binding of [11C]DPA713 (BPND) and [11C]CFT (SUVR) were compared with normal data and between the zonisamide+ and zonisamide− PD groups. The cerebral [11C]DPA713 BPND increased with time predominantly over the parieto-occipital region in PD patients. Comparison of the zonisamide+ group with the zonisamide− group showed lower levels in the cerebral [11C]DPA713 BPND in the zonisamide+ group. While the striatal [11C]CFT SUVR decreased longitudinally, the [11C]CFT SUVR in the nucleus accumbens showed a higher binding in the zonisamide+ group. A significant annual increase in attention score were found in the zonisamide+ group. The current results indicate neuroinflammation proceeds to the whole brain even after anti-parkinsonian therapy, but zonisamide coadministration might have the potential to ameliorate proinflammatory responses, exerting a neuroprotective effect in more damaged nigrostriatal regions with enhanced attention in PD. |
| first_indexed | 2024-03-07T15:04:23Z |
| format | Article |
| id | doaj.art-7bda0839a93d4944b4eb2e8f546e1b3b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:04:23Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-7bda0839a93d4944b4eb2e8f546e1b3b2024-03-05T18:58:22ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-55233-zNeuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET studyTatsuhiro Terada0Tomoyasu Bunai1Takanori Hashizume2Takashi Matsudaira3Masamichi Yokokura4Hirotsugu Takashima5Takashi Konishi6Tomokazu Obi7Yasuomi Ouchi8Department of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of MedicineDepartment of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of MedicineLaboratory of Drug Metabolism and Pharmacokinetics, Faculty of Pharmacy, Osaka Ohtani UniversityDepartment of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of MedicineDepartment of Psychiatry, Hamamatsu University School of MedicineDepartment of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of MedicineDepartment of Neurology, Japanese Red Cross Shizuoka HospitalDepartment of Neurology, Shizuoka Institute of Epilepsy and Neurological DisordersDepartment of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of MedicineAbstract The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson’s disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1–2), and age-matched normal subjects. PD patients were randomly divided into two groups: one (zonisamide+) that did and one (zonisamide−) that did not undergo zonisamide therapy. Annual changes in neuroinflammation ([11C]DPA713 PET), dopamine transporter availability ([11C]CFT PET) and clinical severity were examined. Voxelwise differentiations in the binding of [11C]DPA713 (BPND) and [11C]CFT (SUVR) were compared with normal data and between the zonisamide+ and zonisamide− PD groups. The cerebral [11C]DPA713 BPND increased with time predominantly over the parieto-occipital region in PD patients. Comparison of the zonisamide+ group with the zonisamide− group showed lower levels in the cerebral [11C]DPA713 BPND in the zonisamide+ group. While the striatal [11C]CFT SUVR decreased longitudinally, the [11C]CFT SUVR in the nucleus accumbens showed a higher binding in the zonisamide+ group. A significant annual increase in attention score were found in the zonisamide+ group. The current results indicate neuroinflammation proceeds to the whole brain even after anti-parkinsonian therapy, but zonisamide coadministration might have the potential to ameliorate proinflammatory responses, exerting a neuroprotective effect in more damaged nigrostriatal regions with enhanced attention in PD.https://doi.org/10.1038/s41598-024-55233-zParkinson’s disease (PD)NeuroinflammationDopamine transporterZonisamidePositron emission tomography |
| spellingShingle | Tatsuhiro Terada Tomoyasu Bunai Takanori Hashizume Takashi Matsudaira Masamichi Yokokura Hirotsugu Takashima Takashi Konishi Tomokazu Obi Yasuomi Ouchi Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study Scientific Reports Parkinson’s disease (PD) Neuroinflammation Dopamine transporter Zonisamide Positron emission tomography |
| title | Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study |
| title_full | Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study |
| title_fullStr | Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study |
| title_full_unstemmed | Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study |
| title_short | Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study |
| title_sort | neuroinflammation following anti parkinsonian drugs in early parkinson s disease a longitudinal pet study |
| topic | Parkinson’s disease (PD) Neuroinflammation Dopamine transporter Zonisamide Positron emission tomography |
| url | https://doi.org/10.1038/s41598-024-55233-z |
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