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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

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 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

Authors:
 [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
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE; National Aeronautics and Space Administration (NASA); Stony Brook University
OSTI Identifier:
1259274
Grant/Contract Number:  
NNX11AO89; NNAX13AD74G; NNX13AJ01
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 10; Journal Issue: 7; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.

Citation Formats

Suresh Kumar, M. A., Peluso, Michael, Chaudhary, Pankaj, Dhawan, Jasbeer, Beheshti, Afshin, Manickam, Krishnan, Thapar, Upasna, Pena, Louis, Natarajan, Mohan, Hlatky, Lynn, Demple, Bruce, and Naidu, Mamta. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1. United States: N. p., 2015. Web. doi:10.1371/journal.pone.0133016.
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. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1. United States. doi:10.1371/journal.pone.0133016.
Suresh Kumar, M. A., Peluso, Michael, Chaudhary, Pankaj, Dhawan, Jasbeer, Beheshti, Afshin, Manickam, Krishnan, Thapar, Upasna, Pena, Louis, Natarajan, Mohan, Hlatky, Lynn, Demple, Bruce, and Naidu, Mamta. Fri . "Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1". United States. doi:10.1371/journal.pone.0133016. https://www.osti.gov/servlets/purl/1259274.
@article{osti_1259274,
title = {Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1},
author = {Suresh Kumar, M. A. and Peluso, Michael and Chaudhary, Pankaj and Dhawan, Jasbeer and Beheshti, Afshin and Manickam, Krishnan and Thapar, Upasna and Pena, Louis and Natarajan, Mohan and Hlatky, Lynn and Demple, Bruce and Naidu, Mamta},
abstractNote = {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},
doi = {10.1371/journal.pone.0133016},
journal = {PLoS ONE},
number = 7,
volume = 10,
place = {United States},
year = {2015},
month = {7}
}

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    Works referencing / citing this record:

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    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
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    • Chang, P-W; Zhang, Q-M; Takatori, K.
    • International Journal of Radiation Biology, Vol. 81, Issue 2
    • DOI: 10.1080/09553000500103009

    Managing the cognitive effects of brain tumor radiation therapy
    journal, November 2006

    • Butler, Jerome M.; Rapp, Stephen R.; Shaw, Edward G.
    • Current Treatment Options in Oncology, Vol. 7, Issue 6
    • DOI: 10.1007/s11864-006-0026-5

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    journal, February 2008

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    • DOI: 10.1093/nar/gkn118

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    • Dianov, Grigory L.; O'Neill, Peter; Goodhead, Dudley T.
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    • DOI: 10.1002/bies.1104

    Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice
    journal, August 2004


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    Effects of heavy particle irradiation and diet on object recognition memory in rats
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    • Shihabuddin, Lamya S.; Ray, Jasodhara; Gage, Fred H.
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    • DOI: 10.1006/exnr.1997.6697

    Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks
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