Neurochemical Research

, Volume 36, Issue 6, pp 1017–1026

Increased Spontaneous Apoptosis of Rat Primary Neurospheres In Vitro After Experimental Autoimmune Encephalomyelitis

  • Mir Sajad
  • Jamil Zargan
  • Jyoti Sharma
  • Raman Chawla
  • Rajesh Arora
  • Sadiq Umar
  • Haider A. Khan
Original Paper

DOI: 10.1007/s11064-011-0441-2

Cite this article as:
Sajad, M., Zargan, J., Sharma, J. et al. Neurochem Res (2011) 36: 1017. doi:10.1007/s11064-011-0441-2

Abstract

Survival of neuronal progenitors (NPCs) is a critical determinant of the regenerative capacity of brain following cellular loss. Herein, we report for the first time, the increased spontaneous apoptosis of the first acute phase of Experimental Autoimmune Encephalomyelitis (EAE) derived neurospheres in vitro. Neuronal as well as oligodendroglial loss occurs during experimental autoimmune encephalomyelitis (EAE). This loss is replenished spontaneously by the concomitant increase in the NPC proliferation evidenced by the presence of thin myelin sheaths in the remodeled lesions. However, remyelination depends upon the survival of NPCs and their lineage specific differentiation. We observed significant increase (P < 0.001) in number of BrdU (+) cells in ependymal subventricular zone (SVZ) in EAE rats. EAE derived NPCs showed remarkable increase in S-phase population which was indeed due to the decrease in G-phase progeny suggesting activation of neuronal progenitor cells (NPCs) from quiescence. However, EAE derived neurospheres showed limited survival in vitro which was mediated by the significantly (P < 0.01) depolarized mitochondria, elevated Caspase-3 (P < 0.001) and fragmentation of nuclear DNA evidenced by single cell gel electrophoresis. Our results suggest EAE induced spontaneous apoptosis of NPCs in vitro which may increase the possibility of early stage cell death in the negative regulation of the proliferative cell number and may explain the failure of regeneration in human multiple sclerosis.

Keywords

EAE Ventricular proliferation NPC apoptosis DNA fragmentation Remyelination 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mir Sajad
    • 1
  • Jamil Zargan
    • 1
  • Jyoti Sharma
    • 3
  • Raman Chawla
    • 2
  • Rajesh Arora
    • 3
  • Sadiq Umar
    • 1
  • Haider A. Khan
    • 1
  1. 1.Clinical Toxicology Laboratory (Formerly Developmental Toxicology Laboratory), Department of Medical Elementology and Toxicology (Sponsored by DST-Fund for the Improvement of Science and Technology and UGC-Special Assistance Program)Jamia Hamdard (Hamdard University)New DelhiIndia
  2. 2.Division of CBRN DefenceInstitute of Nuclear Medicine and Allied Sciences (INMAS) DRDONew DelhiIndia
  3. 3.Department of Radiation BiologyInstitute of Nuclear Medicine and Allied Sciences (INMAS) DRDONew DelhiIndia

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