Neural progenitor cells resist excitatory amino acid-induced neurotoxicity.
The applications of neural progenitor cells in clinical therapy for neural degeneration, such as Parkinson's disease, Huntington's disease, and cerebral infarction, have long been explored widely. It had been suggested that these cells may block the apoptosis of ischemia-induced neuronal damage and may themselves resist neurotoxic factors. In the present study, neural progenitor cells derived from the cortex of rodent embryos were cultured with the mitogenic agent epidermal growth factor. It was observed that these progenitor cells could self-renew and differentiate into a number of types of neurons and glial cells. By using sodium nitroprusside, glutamate, and N-methyl-D-aspartate, these neural progenitor cells were shown to have a higher resistance to neurotoxicity induced by these drugs compared with primary neuronal cells. However, the release of nitric oxide in response to glutamate by these neural progenitor cells was similar to the released by primary neuronal cells. Also, when the glutamate-stimulated increase in intracellular free Ca(2+) concentration was measured, stimulation of the glutamate receptors could not induce a significant influx of Ca(2+) into these progenitor cells until they differentiated. Our results suggest that the resistance of neural progenitor cells to neurotoxicity may be partially due to a lack of response to glutamate. In addition, some progenitor-generated neurotrophic factors may contribute to the resistance of these cells to nitric oxide-induced neurotoxicity.
Hsieh
Wen-Ya
WY
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Hsieh
Yi-Lin
YL
Liu
Demeral David
DD
Yang
San-Nan
SN
Wu
Jian-Nan
JN
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D010694:Lactase-Phlorizin Hydrolase / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017942:Nitric Acid / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D018846:Excitatory Amino Acids; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D009573:Nitrites; D018698:Glutamic Acid; D017942:Nitric Acid; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D010694:Lactase-Phlorizin Hydrolase; D010751:Phosphopyruvate Hydratase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester