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Metabolic Brain Disease

, Volume 33, Issue 3, pp 855–868 | Cite as

ER stress and genomic instability induced by gamma radiation in mice primary cultured glial cells

  • Jit Chatterjee
  • Rajesha K. Nairy
  • Jaldeep Langhnoja
  • Ashutosh Tripathi
  • Rajashekhar K. Patil
  • Prakash P. Pillai
  • Mohammed S. Mustak
Original Article

Abstract

Ionizing radiation induces various pathophysiological conditions by altering central nervous system (CNS) homeostasis, leading to neurodegenerative diseases. However, the potential effect of ionizing radiation response on cellular physiology in glial cells is unclear. In the present study, micronucleus test, comet assay, and RT-PCR were performed to investigate the potential effect of gamma radiation in cultured oligodendrocytes and astrocytes with respect to genomic instability, Endoplasmic Reticulum (ER) stress, and inflammation. Further, we studied the effect of alteration in ER stress specific gene expression in cortex post whole body radiation in mice. Results showed that exposure of gamma radiation of 2Gy in-vitro cultured astrocytes and oligodendrocytes and 7Gy in-vivo induced ER stress and Inflammation along with profuse DNA damage and Chromosomal abnormality. Additionally, we observed downregulation of myelin basic protein levels in cultured oligodendrocytes exposed to radiation. The present data suggests that ER stress and pro inflammatory cytokines serve as the major players in inducing glial cell dysfunction post gamma irradiation along with induction of genomic instability. Taken together, these results indicate that ER stress, DNA damage, and inflammatory pathways may be critical events leading to glial cell dysfunction and subsequent cell death following exposure to ionizing radiation.

Keywords

Gamma radiation Astrocytes Oligodendrocytes DNA damage Inflammation ER stress 

Abbreviations

Bcl 2

B-cell lymphoma 2

BIP

Binding immunoglobulin protein

CASP

Comet assay software project

CCK

Cell Counting Kit

DAPI

4′,6-diamidino-2-phenylindole

DMEM

Dulbecco′s modified eagle′s medium

DMSO

Dimethyl sulfoxide

DNA

Deoxyribonucleic acid

FBS

Fetal bovine serum

FITC

Fluorescein isothiocyanate

Gadd153

DNA damage-inducible gene 153

GFAP

Glial fibrillary acidic protein

Gy

Gray

MMW

Millimeter wave

PGE 2

Prostaglandin E2

RT-PCR

Reverse transcription polymerase chain reaction

TRITC

Tetramethylrhodamine

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Applied ZoologyMangalore UniversityMangaloreIndia
  2. 2.Department of PhysicsP.A College of EngineeringMangaloreIndia
  3. 3.Division of Neurobiology, Department of ZoologyMaharaja Sayajirao University of BarodaVadodaraIndia

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