Neurotoxicity screening in a multipotent neural stem cell line established from the mouse brain.
Neural stem cells (NSCs) have mainly been applied to neurodegeneration in some medically intractable neurologic diseases. In this study, we established a novel NSC line and investigated the cytotoxic responses of NSCs to exogenous neurotoxicants, glutamates and reactive oxygen species (ROS). A multipotent NSC line, B2A1 cells, was established from long-term primary cultures of oligodendrocyte-enriched cells from an adult BALB/c mouse brain. B2A1 cells could be differentiated into neuronal, astrocytic and oligodendroglial lineages. The cells also expressed genotypic mRNA messages for both neural progenitor cells and differentiated neuronoglial cells. B2A1 cells treated with hydrogen peroxide and L-buthionine-(S,R)-sulfoximine underwent 30-40% cell death, while B2A1 cells treated with glutamate and kainate showed 25-35% cell death. Cytopathologic changes consisting of swollen cell bodies, loss of cytoplasmic processes, and nuclear chromatin disintegration, developed after exposure to both ROS and excitotoxic chemicals. These results suggest that B2A1 cells may be useful in the study of NSC biology and may constitute an effective neurotoxicity screening system for ROS and excitotoxic chemicals.
Choi
Yong-Soo
YS
Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
Lee
Min-Cheol
MC
Kim
Hyung-Seok
HS
Lee
Kyung-Hwa
KH
Park
Yeoung-Geol
YG
Kim
Hyun-Kyung
HK
Jeong
Han-Seong
HS
Kim
Myeong-Kyu
MK
Woo
Young-Jong
YJ
Kim
Seung-Up
SU
Ryu
Jae-Kyu
JK
Choi
Hyun-Beom
HB
D000818:Animals; D001921:Brain / Q000166:cytology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D016207:Cytokines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D036341:Intercellular Signaling Peptides and Proteins; D009498:Neurotoxins; D016877:Oxidants; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D007608:Kainic Acid