COGNITIVE DISTURBANCES AND THE STATE OF BRAIN GLIAL CELLS IN MICE EXPOSED TO FRACTIONATED WHOLE-BRAIN IRRADIATION

Purpose: To investigate the effect of fractionated whole-brain γ-irradiation at a cumulative dose 20 Gy on cognitive functions, state brain glial cells and expression multiple cytokines in mice 2 months after exposure. Material methods: Male C57Bl/6 were exposed to head with 5 doses 4 Gy. Two irradiation behavior functions animals assessed. After isolation from brains content resting activated microglia, microglial M1- M2-phenotype, astrocytes, proliferating evaluated, hippocampal mRNA levels pro- anti-inflammatory (TNFα, IL-1β, IL-6, IL-4, TGFβ) determined. Results: It was shown that didn’t alter locomotor activity associative (context fear) memory, but reduced episodic memory novel object recognition test (discrimination index 0.44 ± 0.08 и 0.02 0.09 control irradiated groups, respectively) spatial Morris water maze (time target quadrant 46,8 2,4 % 37,4 2,8 respectively). Exposure γ-radiation significantly contents (Iba1+) astrocytes (GFAP+) concurrent 2.5 times increase proportion microglia (from 2.0 0.2 4.9 0.5 mice), changed / M2-microglia ratio decreased number (BrdU+) (BrdU+/Iba1+). An level pro-inflammatory cytokine TNFα, decrease TGFβ IL-4 detected hippocampus irradiation. Conclusion: We show reduces Cognitive dysfunctions are associated neuroinflammation characterized by increasing altered profile.