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Title: Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [4];  [2];  [5];  [6];  [7];  [5];  [2];  [6];  [2]
  1. Columbia Univ., New York, NY (United States)
  2. Tufts Univ. School of Medicine, Boston, MA (United States)
  3. Queen's Univ., Belfast, Northern Ireland (United Kingdom)
  4. Stony Brook Univ., NY (United States)
  5. Univ. of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX (United States)
  6. Stony Brook Univ., NY (United States). Dept. of Pharmacological Sciences
  7. Brookhaven National Lab. (BNL), Upton, NY (United States). Dept. of Biosciences

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 Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE; National Aeronautics and Space Administration (NASA); Stony Brook University
Grant/Contract Number:
NNX11AO89; NNAX13AD74G; NNX13AJ01
OSTI ID:
1259274
Journal Information:
PLoS ONE, Vol. 10, Issue 7; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

References (49)

The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: Feasibility and acute toxicity journal November 2004
Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function journal July 2008
Radiation Resistance in Glioma Cells Determined by DNA Damage Repair Activity of Ape1/Ref-1 journal January 2010
Radiation Response of Neural Precursor Cells journal January 2007
Dynamic changes in N-methyl-D-aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits journal March 2004
Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice journal August 2004
DNA repair of clustered lesions in mammalian cells: involvement of non-homologous end-joining journal July 2008
Managing the cognitive effects of brain tumor radiation therapy journal November 2006
Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance journal August 2005
FGF-2 Is Sufficient to Isolate Progenitors Found in the Adult Mammalian Spinal Cord journal December 1997
Persistent region-dependent neuroinflammation, NMDA receptor loss and atrophy in an animal model of penetrating brain injury journal May 2012
Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors journal June 2010
Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli journal February 2005
Overview of clinical experiences on carbon ion radiotherapy at NIRS journal December 2004
A new look at glutamate and ischemia: NMDA agonist improves long-term functional outcome in a rat model of stroke journal November 2011
Apurinic/apyrimidinic endonuclease 1 is a key modulator of aluminum-induced neuroinflammation journal March 2013
The effects of proton exposure on neurochemistry and behavior journal January 2004
Interaction of Miracil D with double-stranded poly(adenylic acid).poly(uridylic acid) journal April 1974
Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat journal January 2005
Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress journal April 2003
Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: A possible late effect of therapy journal January 1991
Roles of ES Cell-Derived Gliogenic Neural Stem/Progenitor Cells in Functional Recovery after Spinal Cord Injury journal November 2009
Radiation-induced Apoptosis of Oligodendrocytes in Vitro journal January 1992
The adaptive imbalance in base excision–repair enzymes generates microsatellite instability in chronic inflammation journal December 2003
The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation journal February 2004
Distinct Roles of Ape1 Protein in the Repair of DNA Damage Induced by Ionizing Radiation or Bleomycin journal November 2010
Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells journal February 2005
Irradiation induces neural precursor-cell dysfunction journal August 2002
Radiation-Induced Cognitive Impairments are Associated with Changes in Indicators of Hippocampal Neurogenesis journal July 2004
A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data journal November 1988
Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain journal October 2006
Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks journal April 2005
Human abasic endonuclease action on multilesion abasic clusters: implications for radiation-induced biological damage journal February 2008
Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells journal December 2005
Efficient Production of Reactive Oxygen Species in Neural Precursor Cells after Exposure to 250 MeV Protons journal October 2005
Recovery Capacity of Glial Progenitors after In Vivo Fission-Neutron or X Irradiation: Age Dependence, Fractionation and Low-Dose-Rate Irradiations journal June 2005
Securing genome stability by orchestrating DNA repair: removal of radiation-induced clustered lesions in DNA journal January 2001
Mammalian Neural Stem Cells journal February 2000
Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat journal January 2005
Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System journal January 1999
A Novel Role of Lactosylceramide in the Regulation of Lipopolysaccharide/Interferon- -Mediated Inducible Nitric Oxide Synthase Gene Expression: Implications for Neuroinflammatory Diseases journal June 2004
Physiopathology of radiation-induced neurotoxicity journal October 2011
Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord journal March 2000
DNA-polymerase α, β, δ and ε activities in isolated neuronal and astroglial cell fractions from developing and aging rat cerebral cortex journal October 2002
Effects of heavy particle irradiation and diet on object recognition memory in rats journal April 2009
Elevated Expression of APE1/Ref-1 and its Regulation on IL-6 and IL-8 in Bone Marrow Stromal Cells of Multiple Myeloma journal October 2010
The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation journal February 2004
The adaptive imbalance in base excision–repair enzymes generates microsatellite instability in chronic inflammation journal December 2003
In vivo Recombination After Chronic Damage Exposure Falls to Below Spontaneous Levels in “Recombomice” journal October 2004

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