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

Suresh Kumar MA, Peluso M, Chaudhary P, Dhawan J, Beheshti A, Manickam K, Thapar U, Pena L, Natarajan M, Hlatky L, Demple B, Naidu M - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Radiological Research, Columbia University, New York, New York, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Cognition testing of control, protons (1 Gy of 250 MeV protons) (P-irr) and HZE exposed (0.5 Gy Fe/ Si) rats was performed at 6 months of post exposure.T test showed a significant difference between the Fe irr versus control group (p<0.002). 10 rats were analyzed per fraction, with 40 rats per ion (30 + 10 controls).
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pone.0133016.g006: Cognition testing of control, protons (1 Gy of 250 MeV protons) (P-irr) and HZE exposed (0.5 Gy Fe/ Si) rats was performed at 6 months of post exposure.T test showed a significant difference between the Fe irr versus control group (p<0.002). 10 rats were analyzed per fraction, with 40 rats per ion (30 + 10 controls).

Mentions: Animals were also tested in the object recognition task at six months after protons and HZE exposure. Fe irradiated rats showed most significant deficit with single dose and lower deficit with fractionation where as Protons as well as Si showed some trend towards more deficits with fractionation, although the data with Si NORT was most variable (Fig 6). Statistical analysis showed a significant difference only between the Fe-irradiated versus control group (p<0.0011 for single fraction and p<0.05 for two fractions). The single dose of Fe being most detrimental is expected with higher mass of Fe versus Si or Protons. These results are limited owing to the number of rats used (10/ fraction), as well as latent time points where with aged rats, we tend to lose 1–2 rats to premature sacrifice due to sickness.


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

Suresh Kumar MA, Peluso M, Chaudhary P, Dhawan J, Beheshti A, Manickam K, Thapar U, Pena L, Natarajan M, Hlatky L, Demple B, Naidu M - PLoS ONE (2015)

Cognition testing of control, protons (1 Gy of 250 MeV protons) (P-irr) and HZE exposed (0.5 Gy Fe/ Si) rats was performed at 6 months of post exposure.T test showed a significant difference between the Fe irr versus control group (p<0.002). 10 rats were analyzed per fraction, with 40 rats per ion (30 + 10 controls).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514622&req=5

pone.0133016.g006: Cognition testing of control, protons (1 Gy of 250 MeV protons) (P-irr) and HZE exposed (0.5 Gy Fe/ Si) rats was performed at 6 months of post exposure.T test showed a significant difference between the Fe irr versus control group (p<0.002). 10 rats were analyzed per fraction, with 40 rats per ion (30 + 10 controls).
Mentions: Animals were also tested in the object recognition task at six months after protons and HZE exposure. Fe irradiated rats showed most significant deficit with single dose and lower deficit with fractionation where as Protons as well as Si showed some trend towards more deficits with fractionation, although the data with Si NORT was most variable (Fig 6). Statistical analysis showed a significant difference only between the Fe-irradiated versus control group (p<0.0011 for single fraction and p<0.05 for two fractions). The single dose of Fe being most detrimental is expected with higher mass of Fe versus Si or Protons. These results are limited owing to the number of rats used (10/ fraction), as well as latent time points where with aged rats, we tend to lose 1–2 rats to premature sacrifice due to sickness.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Radiological Research, Columbia University, New York, New York, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus