Scientific Reports (Feb 2024)

Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study

  • Tatsuhiro Terada,
  • Tomoyasu Bunai,
  • Takanori Hashizume,
  • Takashi Matsudaira,
  • Masamichi Yokokura,
  • Hirotsugu Takashima,
  • Takashi Konishi,
  • Tomokazu Obi,
  • Yasuomi Ouchi

DOI
https://doi.org/10.1038/s41598-024-55233-z
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 12

Abstract

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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.

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