Low-dose brain radiation: lowering hyperphosphorylated-tau without increasing DNA damage or oncogenic activation.

Autor: Iacono D; DoD/USU Brain Tissue Repository and Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA. diego.iacono.ctr@usuhs.edu.; Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA. diego.iacono.ctr@usuhs.edu.; Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA. diego.iacono.ctr@usuhs.edu.; Neuroscience Program, Department of Anatomy, Physiology and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA. diego.iacono.ctr@usuhs.edu.; The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD, USA. diego.iacono.ctr@usuhs.edu.; Neurodegeneration Disorders Clinic, National Institute of Neurological Disorders and Stroke, NINDS, NIH, Bethesda, MD, USA. diego.iacono.ctr@usuhs.edu., Murphy EK; DoD/USU Brain Tissue Repository and Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA.; Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD, USA., Stimpson CD; DoD/USU Brain Tissue Repository and Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA.; Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD, USA., Perl DP; DoD/USU Brain Tissue Repository and Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA.; Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA., Day RM; Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 30; Vol. 13 (1), pp. 21142. Date of Electronic Publication: 2023 Nov 30.
DOI: 10.1038/s41598-023-48146-w
Abstrakt: Brain radiation has been medically used to alter the metabolism of cancerous cells and induce their elimination. Rarely, though, brain radiation has been used to interfere with the pathomechanisms of non-cancerous brain disorders, especially neurodegenerative disorders. Data from low-dose radiation (LDR) on swine brains demonstrated reduced levels of phosphorylated-tau (CP13) and amyloid precursor protein (APP) in radiated (RAD) versus sham (SH) animals. Phosphorylated-tau and APP are involved in Alzheimer's disease (AD) pathogenesis. We determined if the expression levels of hyperphosphorylated-tau, 3R-tau, 4R-tau, synaptic, intraneuronal damage, and DNA damage/oncogenic activation markers were altered in RAD versus SH swine brains. Quantitative analyses demonstrated reduced levels of AT8 and 3R-tau in hippocampus (H) and striatum (Str), increased levels of synaptophysin and PSD-95 in frontal cortex (FCtx), and reduced levels of NF-L in cerebellum (CRB) of RAD versus SH swine. DNA damage and oncogene activation markers levels did not differ between RAD and SH animals, except for histone-H3 (increased in FCtx and CRB, decreased in Str), and p53 (reduced in FCtx, Str, H and CRB). These findings confirm the region-based effects of sLDR on proteins normally expressed in larger mammalian brains and support the potential applicability of LDR to beneficially interfere against neurodegenerative mechanisms.
(© 2023. The Author(s).)
Databáze: MEDLINE
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