Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Neuroinflammation Année : 2022

Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats

Résumé

Abstract Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aβ aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ − 60 to − 80%, P < 0.01 ; soluble and aggregated forms of Aβ 40 , Aβ 42 , and Aβ oligomers ). Interestingly, we showed for the first time that sAPPα levels were improved by the treatment, showing a higher activation of the non-amyloidogenic pathway, that could favor neuronal survival. The current evidence confirms the capacity of LD-RT to successfully modulate two pathological hallmarks of AD, namely amyloid and neuroinflammation, when applied before symptoms onset.

Domaines

Neurosciences

Dates et versions

hal-03949137 , version 1 (20-01-2023)

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Citer

Kelly Ceyzériat, Thomas Zilli, Philippe Millet, Nikolaos Koutsouvelis, Giovanna Dipasquale, et al.. Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats. Journal of Neuroinflammation, 2022, 19 (1), pp.311. ⟨10.1186/s12974-022-02673-x⟩. ⟨hal-03949137⟩
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