title: Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1.
abstract: 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.
authors.affiliation: Center for Radiological Research, Columbia University, New York, New York, United States of America.
authors.forename: M A
authors.initials: MA
authors.lastname: Suresh Kumar
authors.affiliation: GeneSys Research Institute/ Center for Cancer Systems Biology at Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Peluso
authors.affiliation: Centre for Cancer Research and Cell Biology, Queens University, Belfast, United Kingdom.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Chaudhary
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Jasbeer
authors.initials: J
authors.lastname: Dhawan
authors.affiliation: GeneSys Research Institute/ Center for Cancer Systems Biology at Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Afshin
authors.initials: A
authors.lastname: Beheshti
authors.affiliation: Department of Pathology, UTHSCSA, San Antonio, Texas, United States of America.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Manickam
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Upasna
authors.initials: U
authors.lastname: Thapar
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, New York, United States of America.
authors.forename: Louis
authors.initials: L
authors.lastname: Pena
authors.affiliation: Department of Pathology, UTHSCSA, San Antonio, Texas, United States of America.
authors.forename: Mohan
authors.initials: M
authors.lastname: Natarajan
authors.affiliation: GeneSys Research Institute/ Center for Cancer Systems Biology at Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Hlatky
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Bruce
authors.initials: B
authors.lastname: Demple
authors.affiliation: GeneSys Research Institute/ Center for Cancer Systems Biology at Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Mamta
authors.initials: M
authors.lastname: Naidu
mesh_terms: D000818:Animals; D015415:Biomarkers; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000069079:Radiation Exposure; D011839:Radiation, Ionizing; D051381:Rats; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase