Low-moderate dose whole-brain γ-ray irradiation modulates the expressions of glial fibrillary acidic protein and intercellular adhesion molecule-1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model

Neurobiol Aging. 2023 Dec:132:175-184. doi: 10.1016/j.neurobiolaging.2023.06.015. Epub 2023 Jun 29.

Abstract

The anti-inflammatory efficacy of radiation therapy (RT) with single fractions below 1.0 Gy has been demonstrated in Alzheimer's disease mouse models. As neuroinflammation is also a major pathological feature of Parkinson's disease (PD), RT may also be effective in PD treatment. Therefore, this study aimed to investigate the anti-inflammatory effect of low-moderate dose RT (LMDRT, 0.6 Gy/single dose, for 5 days) exposure in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally, for 5 consecutive days)-induced PD mouse model. Importantly, LMDRT reduced the levels of glial fibrillary acidic protein and intercellular adhesion molecule-1 (CD54) in the striatum region, which increased following MPTP administration. LMDRT also modulated inflammatory gene expression patterns in the substantia nigra region of the MPTP-treated mice. However, LMDRT had no direct effects on the severe loss of dopaminergic neurons and impaired motor behavior in the rotarod test. These results indicate that LMDRT has anti-inflammatory effects by modulating neuroinflammatory factors, including glial fibrillary acidic protein and intercellular adhesion molecule-1, but showed no behavioral improvements or neuroprotection in the MPTP-induced mouse model of PD.

Keywords: GFAP; ICAM-1 (CD54); Low-moderate dose radiation therapy; Neuroinflammation; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / metabolism
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / therapeutic use
  • Animals
  • Brain* / metabolism
  • Brain* / radiation effects
  • Disease Models, Animal
  • Dopaminergic Neurons / pathology
  • Glial Fibrillary Acidic Protein* / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Adhesion Molecule-1 / pharmacology
  • Intercellular Adhesion Molecule-1 / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / radiotherapy
  • Substantia Nigra / metabolism

Substances

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Glial Fibrillary Acidic Protein
  • Intercellular Adhesion Molecule-1