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:
-
- Columbia Univ., New York, NY (United States)
- Tufts Univ. School of Medicine, Boston, MA (United States)
- Queen's Univ., Belfast, Northern Ireland (United Kingdom)
- Stony Brook Univ., NY (United States)
- Univ. of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX (United States)
- Stony Brook Univ., NY (United States). Dept. of Pharmacological Sciences
- Brookhaven National Lab. (BNL), Upton, NY (United States). Dept. of Biosciences
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (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:
- Journal Article: 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. https://doi.org/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. 2015.
"Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1". United States. https://doi.org/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},
url = {https://www.osti.gov/biblio/1259274},
journal = {PLoS ONE},
issn = {1932-6203},
number = 7,
volume = 10,
place = {United States},
year = {Fri Jul 24 00:00:00 EDT 2015},
month = {Fri Jul 24 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: Feasibility and acute toxicity
journal, November 2004
- Beckendorf, Véronique; Guérif, Stéphane; Le Prisé, Elisabeth
- International Journal of Radiation Oncology*Biology*Physics, Vol. 60, Issue 4
The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: Feasibility and acute toxicity
journal, November 2004
- Beckendorf, Véronique; Guérif, Stéphane; Le Prisé, Elisabeth
- International Journal of Radiation Oncology*Biology*Physics, Vol. 60, Issue 4
Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function
journal, July 2008
- Englander, Ella W.
- Mechanisms of Ageing and Development, Vol. 129, Issue 7-8
Radiation Resistance in Glioma Cells Determined by DNA Damage Repair Activity of Ape1/Ref-1
journal, January 2010
- Naidu, Mamta D.; Mason, James M.; Pica, Raymond V.
- Journal of Radiation Research, Vol. 51, Issue 4
Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function
journal, July 2008
- Englander, Ella W.
- Mechanisms of Ageing and Development, Vol. 129, Issue 7-8
Radiation Response of Neural Precursor Cells
journal, January 2007
- Fike, John R.; Rola, Radoslaw; Limoli, Charles L.
- Neurosurgery Clinics of North America, Vol. 18, Issue 1
Radiation Response of Neural Precursor Cells
journal, January 2007
- Fike, John R.; Rola, Radoslaw; Limoli, Charles L.
- Neurosurgery Clinics of North America, Vol. 18, Issue 1
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
- Biegon, A.; Fry, P. A.; Paden, C. M.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 14
Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice
journal, August 2004
- Rola, Radoslaw; Raber, Jacob; Rizk, Angela
- Experimental Neurology, Vol. 188, Issue 2
DNA repair of clustered lesions in mammalian cells: involvement of non-homologous end-joining
journal, July 2008
- Malyarchuk, S.; Castore, R.; Harrison, L.
- Nucleic Acids Research, Vol. 36, Issue 15
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
DNA repair of clustered lesions in mammalian cells: involvement of non-homologous end-joining
journal, July 2008
- Malyarchuk, S.; Castore, R.; Harrison, L.
- Nucleic Acids Research, Vol. 36, Issue 15
Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance
journal, August 2005
- Harrison, J. F.
- Nucleic Acids Research, Vol. 33, Issue 14
FGF-2 Is Sufficient to Isolate Progenitors Found in the Adult Mammalian Spinal Cord
journal, December 1997
- Shihabuddin, Lamya S.; Ray, Jasodhara; Gage, Fred H.
- Experimental Neurology, Vol. 148, Issue 2
Persistent region-dependent neuroinflammation, NMDA receptor loss and atrophy in an animal model of penetrating brain injury
journal, May 2012
- Grossman, Rachel; Paden, Charles M.; Fry, Pamela A.
- Future Neurology, Vol. 7, Issue 3
Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors
journal, June 2010
- Dhawan, Jasbeer; Benveniste, Helene; Nawrocky, Marta
- NeuroImage, Vol. 51, Issue 2
Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli
journal, February 2005
- Chang, P-W; Zhang, Q-M; Takatori, K.
- International Journal of Radiation Biology, Vol. 81, Issue 2
Overview of clinical experiences on carbon ion radiotherapy at NIRS
journal, December 2004
- Tsujii, Hirohiko; Mizoe, Jun-etsu; Kamada, Tadashi
- Radiotherapy and Oncology, Vol. 73
A new look at glutamate and ischemia: NMDA agonist improves long-term functional outcome in a rat model of stroke
journal, November 2011
- Dhawan, Jasbeer; Benveniste, Helene; Luo, Zhongchi
- Future Neurology, Vol. 6, Issue 6
Apurinic/apyrimidinic endonuclease 1 is a key modulator of aluminum-induced neuroinflammation
journal, March 2013
- Zaky, Amira; Mohammad, Bassma; Moftah, Marie
- BMC Neuroscience, Vol. 14, Issue 1
The effects of proton exposure on neurochemistry and behavior
journal, January 2004
- Shukitt-Hale, B.; Szprengiel, A.; Pluhar, J.
- Advances in Space Research, Vol. 33, Issue 8
Interaction of Miracil D with double-stranded poly(adenylic acid).poly(uridylic acid)
journal, April 1974
- Heller, Michael J.; Tu, Anthony T.; Maciel, Gary E.
- Biochemistry, Vol. 13, Issue 8
Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat
journal, January 2005
- Mothe, A.; Tator, C.
- Neuroscience
Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress
journal, April 2003
- Druzhyna, Nadiya M.; Hollensworth, Scott B.; Kelley, Mark R.
- Glia, Vol. 42, Issue 4
Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: A possible late effect of therapy
journal, January 1991
- Allen, J. C.; Miller, D. C.; Budzilovich, G. N.
- Neurology, Vol. 41, Issue 1
Apurinic/apyrimidinic endonuclease 1 is a key modulator of aluminum-induced neuroinflammation
journal, March 2013
- Zaky, Amira; Mohammad, Bassma; Moftah, Marie
- BMC Neuroscience, Vol. 14, Issue 1
Roles of ES Cell-Derived Gliogenic Neural Stem/Progenitor Cells in Functional Recovery after Spinal Cord Injury
journal, November 2009
- Kumagai, Gentaro; Okada, Yohei; Yamane, Junichi
- PLoS ONE, Vol. 4, Issue 11
Radiation-induced Apoptosis of Oligodendrocytes in Vitro
journal, January 1992
- Vrdoljak, E.; Bill, C. A.; Stephens, L. C.
- International Journal of Radiation Biology, Vol. 62, Issue 4
The adaptive imbalance in base excision–repair enzymes generates microsatellite instability in chronic inflammation
journal, December 2003
- Hofseth, Lorne J.; Khan, Mohammed A.; Ambrose, Mark
- Journal of Clinical Investigation, Vol. 112, Issue 12
The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation
journal, February 2004
- Hofseth, Lorne J.; Khan, Mohammed A.; Ambrose, Mark
- Journal of Clinical Investigation, Vol. 113, Issue 3
Distinct Roles of Ape1 Protein in the Repair of DNA Damage Induced by Ionizing Radiation or Bleomycin
journal, November 2010
- Fung, Hua; Demple, Bruce
- Journal of Biological Chemistry, Vol. 286, Issue 7
Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells
journal, February 2005
- Fukuda, Aya; Fukuda, Hirotsugu; Swanpalmer, Janos
- Journal of Neurochemistry, Vol. 92, Issue 3
Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance
journal, August 2005
- Harrison, J. F.
- Nucleic Acids Research, Vol. 33, Issue 14
Irradiation induces neural precursor-cell dysfunction
journal, August 2002
- Monje, Michelle L.; Mizumatsu, Shinichiro; Fike, John R.
- Nature Medicine, Vol. 8, Issue 9
Radiation-Induced Cognitive Impairments are Associated with Changes in Indicators of Hippocampal Neurogenesis
journal, July 2004
- Raber, Jacob; Rola, Radoslaw; LeFevour, Anthony
- Radiation Research, Vol. 162, Issue 1
A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data
journal, November 1988
- Ennaceur, A.; Delacour, J.
- Behavioural Brain Research, Vol. 31, Issue 1
Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain
journal, October 2006
- Zou, Gang-Ming; Luo, Mei-Hua; Reed, April
- Blood, Vol. 109, Issue 5
Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain
journal, October 2006
- Zou, Gang-Ming; Luo, Mei-Hua; Reed, April
- Blood, Vol. 109, Issue 5
Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks
journal, April 2005
- Ennaceur, A.; Michalikova, S.; Bradford, A.
- Behavioural Brain Research, Vol. 159, Issue 2
Human abasic endonuclease action on multilesion abasic clusters: implications for radiation-induced biological damage
journal, February 2008
- Paap, B.; Wilson, D. M.; Sutherland, B. M.
- Nucleic Acids Research, Vol. 36, Issue 8
Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells
journal, December 2005
- Fukuda, Aya; Fukuda, Hirotsugu; Swanpalmer, Janos
- Journal of Neurochemistry, Vol. 95, Issue 6
Efficient Production of Reactive Oxygen Species in Neural Precursor Cells after Exposure to 250 MeV Protons
journal, October 2005
- Giedzinski, Erich; Rola, Radoslaw; Fike, John R.
- Radiation Research, Vol. 164, Issue 4
Recovery Capacity of Glial Progenitors after In Vivo Fission-Neutron or X Irradiation: Age Dependence, Fractionation and Low-Dose-Rate Irradiations
journal, June 2005
- Philippo, H.; Winter, E. A. M.; van der Kogel, A. J.
- Radiation Research, Vol. 163, Issue 6
Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells
journal, December 2005
- Fukuda, Aya; Fukuda, Hirotsugu; Swanpalmer, Janos
- Journal of Neurochemistry, Vol. 95, Issue 6
Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks
journal, April 2005
- Ennaceur, A.; Michalikova, S.; Bradford, A.
- Behavioural Brain Research, Vol. 159, Issue 2
Securing genome stability by orchestrating DNA repair: removal of radiation-induced clustered lesions in DNA
journal, January 2001
- Dianov, Grigory L.; O'Neill, Peter; Goodhead, Dudley T.
- BioEssays, Vol. 23, Issue 8
Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat
journal, January 2005
- Mothe, A. J.; Tator, C. H.
- Neuroscience, Vol. 131, Issue 1
Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System
journal, January 1999
- Johansson, Clas B.; Momma, Stefan; Clarke, Diana L.
- Cell, Vol. 96, Issue 1
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
- Pannu, R.
- Journal of Neuroscience, Vol. 24, Issue 26
Human abasic endonuclease action on multilesion abasic clusters: implications for radiation-induced biological damage
journal, February 2008
- Paap, B.; Wilson, D. M.; Sutherland, B. M.
- Nucleic Acids Research, Vol. 36, Issue 8
Physiopathology of radiation-induced neurotoxicity
journal, October 2011
- Fike, J. R.
- Revue Neurologique, Vol. 167, Issue 10
Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord
journal, March 2000
- Horner, Philip J.; Power, Ann E.; Kempermann, Gerd
- The Journal of Neuroscience, Vol. 20, Issue 6
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
- Raji, N. S.; Hari Krishna, T.; Rao, Kalluri Subba
- International Journal of Developmental Neuroscience, Vol. 20, Issue 6
Persistent region-dependent neuroinflammation, NMDA receptor loss and atrophy in an animal model of penetrating brain injury
journal, May 2012
- Grossman, Rachel; Paden, Charles M.; Fry, Pamela A.
- Future Neurology, Vol. 7, Issue 3
A new look at glutamate and ischemia: NMDA agonist improves long-term functional outcome in a rat model of stroke
journal, November 2011
- Dhawan, Jasbeer; Benveniste, Helene; Luo, Zhongchi
- Future Neurology, Vol. 6, Issue 6
Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors
journal, June 2010
- Dhawan, Jasbeer; Benveniste, Helene; Nawrocky, Marta
- NeuroImage, Vol. 51, Issue 2
Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli
journal, February 2005
- Chang, P-W; Zhang, Q-M; Takatori, K.
- International Journal of Radiation Biology, Vol. 81, Issue 2
Effects of heavy particle irradiation and diet on object recognition memory in rats
journal, April 2009
- Rabin, Bernard M.; Carrihill-Knoll, Kirsty; Hinchman, Marie
- Advances in Space Research, Vol. 43, Issue 8
Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress
journal, April 2003
- Druzhyna, Nadiya M.; Hollensworth, Scott B.; Kelley, Mark R.
- Glia, Vol. 42, Issue 4
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
- Xie, Jia-Yin; Li, Meng-Xia; Xiang, De-Bing
- Clinical Lymphoma Myeloma and Leukemia, Vol. 10, Issue 5
Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice
journal, August 2004
- Rola, Radoslaw; Raber, Jacob; Rizk, Angela
- Experimental Neurology, Vol. 188, Issue 2
Roles of ES Cell-Derived Gliogenic Neural Stem/Progenitor Cells in Functional Recovery after Spinal Cord Injury
journal, November 2009
- Kumagai, Gentaro; Okada, Yohei; Yamane, Junichi
- PLoS ONE, Vol. 4, Issue 11
Securing genome stability by orchestrating DNA repair: removal of radiation-induced clustered lesions in DNA
journal, January 2001
- Dianov, Grigory L.; O'Neill, Peter; Goodhead, Dudley T.
- BioEssays, Vol. 23, Issue 8
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
Physiopathology of radiation-induced neurotoxicity
journal, October 2011
- Fike, J. R.
- Revue Neurologique, Vol. 167, Issue 10
Interaction of Miracil D with double-stranded poly(adenylic acid).poly(uridylic acid)
journal, April 1974
- Heller, Michael J.; Tu, Anthony T.; Maciel, Gary E.
- Biochemistry, Vol. 13, Issue 8
Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat
journal, January 2005
- Mothe, A. J.; Tator, C. H.
- Neuroscience, Vol. 131, Issue 1
The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation
journal, February 2004
- Hofseth, L. J.
- Journal of Clinical Investigation, Vol. 113, Issue 3
The adaptive imbalance in base excision–repair enzymes generates microsatellite instability in chronic inflammation
journal, December 2003
- Hofseth, Lorne J.; Khan, Mohammed A.; Ambrose, Mark
- Journal of Clinical Investigation, Vol. 112, Issue 12
In vivo Recombination After Chronic Damage Exposure Falls to Below Spontaneous Levels in “Recombomice”
journal, October 2004
- Kovalchuk, Olga; Hendricks, Carrie A.; Cassie, Scott
- Molecular Cancer Research, Vol. 2, Issue 10
Works referencing / citing this record:
Evaluating biomarkers to model cancer risk post cosmic ray exposure
journal, June 2016
- Sridharan, Deepa M.; Asaithamby, Aroumougame; Blattnig, Steve R.
- Life Sciences in Space Research, Vol. 9