Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent NeuroInflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; Dhawan, Jasbeer; Beheshti, Afshin; Manickam, Krishnan; Thapar, Upasna; Pena, Louis; Natarajan, Mohan; Hlatky, Lynn; Demple, Bruce; Naidu, Mamta

Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction of Apurinic Endonuclease-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of protons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. The oligodendrocyte progenitor cells differentiation was skewed with increase in immature oligodendrocytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects.


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Center for Radiological Research
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February 4, 2016