Low-dose gamma radiation does not trigger early Parkinson’s biomarkers in the substantia nigra

A preclinical investigation published in npj Parkinson’s Disease (2025) explored whether sublethal low-dose γ-radiation could induce Parkinson’s disease (PD)-related alterations in the substantia nigra (SN) of large mammals. Conducted at the Uniformed Services University (Bethesda, USA), the study used Göttingen minipigs to model human-like neuroanatomy and radiosensitivity.

Fourteen animals were divided into a radiation group (1.79 Gy total-body γ-radiation) and a sham control group, with brains analyzed 30 days post-exposure for hallmark PD markers. Molecular assays assessed α-synuclein, phosphorylated α-synuclein (pS129), tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and mitochondrial proteins (ATP5A, SDHB, NDUF8), alongside PD-linked genes such as GBA, VPS13C, and Cathepsin D.

No significant differences emerged between irradiated and control groups across molecular, histological, or immunohistochemical parameters. Dopaminergic neuron density, astroglial activation, and mitochondrial homeostasis remained intact. LRRK2 protein was undetectable, consistent with its low baseline expression in the swine substantia nigra. Importantly, no evidence of neuroinflammation, oxidative stress, or neuronal loss was observed, contrasting with prior rodent studies that reported radiation-induced oxidative injury at comparable doses.

The authors highlight that the absence of neuromelanin in pig dopaminergic neurons—unlike in humans—may confer relative resistance to oxidative damage. They suggest that chronic or repeated low-dose exposures may still pose cumulative risks, aligning with epidemiological data linking ionizing radiation to neurodegenerative disease in humans. Scenarios such as radiological accidents, spaceflight radiation, or therapeutic overexposure could represent real-world parallels.

In conclusion, a single 1.79 Gy γ-radiation exposure does not elicit early PD-related molecular or structural effects in the substantia nigra of large mammals. Future research should investigate chronic exposure, behavioral outcomes, and mitochondrial dynamics to clarify potential delayed or synergistic neurodegenerative impacts.

#ParkinsonsDisease #Neurodegeneration #RadiationBiology #DopaminergicNeurons #SubstantiaNigra

Editorial Note

This text was organized with the support of artificial intelligence, but it was critically reviewed and validated by a qualified professional to ensure scientific accuracy and reliability.