γ-Radiation induces region-specific subcellular alterations of amyotrophic lateral sclerosis and frontotemporal dementia markers in swine brain

Low-dose radiation (LDR) effects on the brain have been poorly investigated. Studies have also questioned whether radiation increases ALS risk. We assessed the expression levels of a series of proteins associated with ALS and ALS-FTD in the brains of swine exposed to low-dose radiation to explore this notion. Male Gottingen minipigs were exposed to a single total-body γ-radiation (1.79 Gy). After 28 days, brains from 9 RAD to 6 SH animals were collected. Using neuroanatomically based dissection and Western Blotting, we compared levels of ALS/ALS-FTD markers (SOD1, FUS/TLS, C9orf72, STMN2, ubiquitin, TDP43 (N and C terminal), and pTDP43) in RAD vs. SH animals in frontal cortex (FCtx), striatum (Str), hippocampus (Hip), thalamus/hypothalamus (Thal/Hyp), and cerebellum (Cere). Cytosolic FUS/TLS decreased in the Thal/Hyp and remained unchanged in all other regions; nuclear levels increased in the FCtx and decreased in the Hip of RAD vs. SH. Cytosolic C9orf72 remained unchanged across all brain regions; nuclear levels decreased in the Hip of RAD vs. SH. Cytosolic STMN2 remained unchanged in all brain regions and decreased in the nuclear fraction of the Hip of RAD vs. SH. Cytosolic and nuclear ubiquitin remained unchanged across brain regions, except for an increase in the FCtx. TDP-43 (N and C terminal) levels remained unchanged in cytosolic and nuclear fractions across all brain regions; finally, cytosolic pTDP43 (S403/404) increased in the FCtx, Str and Thal/Hyp of RAD vs. SH. LDR-induced ALS/ALS-FTD-marker changes differ across brain regions and subcellular compartments. These changes are not necessarily associated with increased activation or potentiation of the main molecular processes associated with ALS pathogenesis; surprisingly, they may produce beneficial effects.