title: Increased spontaneous apoptosis of rat primary neurospheres in vitro after experimental autoimmune encephalomyelitis.
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.
authors: Clinical Toxicology Laboratory Formerly Developmental Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard University, New Delhi 110062, India.
authors: Mir
authors: M
authors: Sajad
authors: Jamil
authors: J
authors: Zargan
authors: Jyoti
authors: J
authors: Sharma
authors: Raman
authors: R
authors: Chawla
authors: Rajesh
authors: R
authors: Arora
authors: Sadiq
authors: S
authors: Umar
authors: Haider A
authors: HA
authors: Khan
mesh_terms: D000818:Animals; D017209:Apoptosis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar