Combined Ionizing Radiation Exposure Improves Behavioral Symptoms and Modulates Brain Innate Immune System Activity in the Tau P301S Mice Line

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Viktor S. Kokhan¹, Ruslan A. Ageldinov², Petr K. Anokhin¹, Inna Yu. Shamakina^1,a*

¹“V. P. Serbsky National Medical Research Center of Psychiatry and Narcology”, Ministry of Health of the Russian Federation, 119002 Moscow, Russia

²Scientific Center for Biomedical Technologies, Federal Medical and Biological Agency of Russia, 143442 Svetlye Gory, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received: December 12, 2024; Revised: February 3, 2025; Accepted: March 11, 2025

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Tauopathy is a group of neurodegenerative diseases associated with abnormal phosphorylation and aggregation of microtubule-associated tau protein. There are currently no disease-modifying therapies for the treatment of tauopathies, however, substantial evidence has shown that there is a major role of neuroinflammation in the disease progression. According to the literature, ionizing radiation (IR) may serve as an effective tool for managing neuroinflammation. In this study, we investigated effects of the combined IR (γ-rays and carbon-12 nuclei) on locomotor abilities and microglial activation markers in the brain of Tau P301S mice, a transgenic model for tauopathy. Irradiation resulted in the improvement of behavioral symptoms in mice: increased endurance and locomotor activity in the early symptomatic and terminal stages of the disease, respectively. At the same time, irradiation led to increase in the levels of both pro-inflammatory and anti-inflammatory cytokines in the cerebellum and, to a lesser extent, in the hippocampus of the irradiated animals. The obtained data indicate a significant modulatory effect of IR on the innate immune system, highlighting high potential of radiotherapy as a new strategy for neurodegenerative disease treatment.

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KEY WORDS: ionizing radiation, radiotherapy, tauopathy, motor activity, cerebellum, hippocampus, cytokines

DOI: 10.1134/S0006297924604453

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