Alla V. Rodina

Рецептор колониестимулирующего фактора-1 (CSF1R) обладает тирозинкиназной активностью, в головном мозге он представлен на клетках микроглии, и его активация обеспечивает их репопуляцию. Введение мышам ингибитора CSF1R пексидартиниба (ПД, 40 мг/кг, внутрижелудочно, 7 сут) снижало количество клеток микроглии на 90 %. Облучение головы в дозе 8 Гр приводило через 2 мес к развитию нейровоспаления, о чем свидетельствовало повышение доли активированной микроглии в препаратах клеток мозга, и к нарушению когнитивных функций. Введение ПД перед облучением предотвращало активацию микроглии. При анализе эпизодической памяти в тесте «Распознавание нового объекта» и пространственной гиппокамп-зависимой памяти в тесте «Водный лабиринт Морриса» показано, что снижение количества клеток микроглии перед облучением с помощью ПД обеспечивает сохранение эпизодической и пространственной памяти у облученных мышей.

Currently there are no effective diagnostic methods for the control of neuroinflammation before manifestation of cognitive impairment after head irradiation. The translocator protein (TSPO) is high...

Tissue regeneration following radiotherapy occurs due to the survival and regenerative abilities of tissue stem cells and resident or invading mesenchymal stem cells (MSCs), and their functional characteristics depend significantly on their sensitivity to ionizing radiation. The aim of this work was to study the effect of long-term cultivation of adipose tissue–derived MSCs on their radiosensitivity and the ability to repair DNA double-strand breaks (DSBs). To determine whether in vitro expansion influences the sensitivity of MSCs to low and sublethal doses of γ-radiation, we maintained short- and long-term MSC cultures and analyzed their radiosensitivity at early and late passages. MSCs possessed a high telomerase activity at passage 6 (P6) and an extremely low one at passage 30 (P30). The doubling time of cells by passage 30 decreased by 7 h. MSCs irradiated at P30 demonstrated significantly decreased survival seven days after irradiation at 0.1 and 1 Gy compared with the control and P6 cultures. The clonogenic activity of MSCs irradiated at P30 and P6 was the same. MSC cell cycle analysis at P30 and P6 indicated G₀/G₁ arrest after 24 h, but G₂/M arrest at 6 Gy after seven days. The P30 MSCs were able to repair DNA DSB efficiently after γ-irradiation. Even after irradiation at a dose of 6 Gy, P30 MSCs maintained their ability for adipocyte differentiation and cytokine secretion. These results demonstrate that, after long-term cultivation, adipose tissue-derived MSCs maintain the ability to repair DNA DSB and possess stable functional characteristics and differentiation potential after irradiation, suggesting their resistance to sublethal doses of γ-radiation. They can also retain their functions in the tissue surrounding the irradiated organ.

ABSTRACТ Purpose: To explore if the total body γ-irradiation at a dose of 0.1 Gy 7 days prior to acute mixed γ, n-irradiation of the head at the dose of 1 Gy can reduce the harmful effects of neutron irradiation on the hippocampal functions, neuroinflammation and neurogenesis. Materials and methods: Mice were exposed to γ-radiation alone, mixed γ,n-radiation or combined γ-rays and γ,n-radiation 7 days after γ-irradiation. Two months post-irradiation, mice were tested in Open Field and in the Morris water maze. The content of microglia, astrocytes, proliferating cells and cytokines TGF-β, TNF-α, IL-1β, GFAP levels, hippocampal BDNF, NT-3, NT-4, NGF mRNA expression were evaluated. Results: Two months after combined irradiation, we observed impaired hippocampus-dependent cognition, which was not detected in mice exposed to γ,n-irradiation. Combined exposure and γ,n-irradiation led to a significant increase in the level of activated microglia and astrocytes in the brains. The level of pro- and anti-inflammatory cytokines in the brain and hippocampal neurotrophine's genes changed differenly after the combined exposure and γ,n-irradiation. The quantity of DCX-positive cells was reduced after γ,n-irradiation exposer alone, but increased after combined irradiation. Conclusions: Our results indicate radio-adaptive responses in brains of mice that were exposed to low-dose gamma irradiation 7 days prior to acute 1 Gy γ,n-irradiation.