Glutamate enhances survival and proliferation of neural progenitors derived from the subventricular zone.
Extracellular glutamate levels increase as a consequence of perinatal hypoxia/ischemia, causing the death of neurons and oligodendrocytes. Precursors in the subventricular zone (SVZ) also die following perinatal hypoxia/ischemia; therefore we hypothesized that glutamate would stimulate the death of neural precursors. Here we demonstrate using calcium imaging that SVZ derived neural stem/progenitor cells respond to both ionotropic and metabotropic excitatory amino acids. Therefore, we tested the effects of high levels of glutamate receptor agonists on the proliferation, survival, and differentiation of SVZ derived neural stem/progenitor cells in vitro. We show that high levels of glutamate, up to 1 mM, are not toxic to neural precursor cultures. In fact, stimulation of either the kainate receptor or group 2 metabotropic glutamate receptors (group 2 mGluR) reduces basal levels of apoptosis and increases neural precursor proliferation. Furthermore, group 2 mGluR activation expands the number of multipotent progenitor cells present in these cultures while maintaining equivalent mature cell production. We conclude that the glutamate released following perinatal hypoxia/ischemia may act to acutely promote the proliferation of multipotent precursors in the subventricular zone.
Brazel
C Y
CY
Stem Cell Biology Unit, Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224, USA.
Nuñez
J L
JL
Yang
Z
Z
Levison
S W
SW
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009336:Necrosis; D020932:Nerve Growth Factor / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
D002118:Calcium; D016222:Fibroblast Growth Factor 2; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D020932:Nerve Growth Factor; D009414:Nerve Growth Factors; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; C495041:Gdnf protein, rat; C108822:metabotropic glutamate receptor 2