To date, attempts to isolate stem cells from the hippocampus have produced mixed results, leading the authors to speculate that a latent population of cells in the hippocampus only exhibits stem-cell-like properties upon some kind of stimulation. To investigate this possibility, they stimulated dissociated hippocampal cultures with KCl and examined the formation of neurospheres — clusters of cells formed by dividing progenitors. The stimulated cultures generated more neurospheres and, importantly, generated a small subpopulation of large neurospheres that could be repeatedly dissociated and re-plated to produce more neurospheres — a property that is typically attributed to stem cells. Further experiments revealed that the stem cells are normally slow-dividing, and that their activation relies on the activity of L-type Ca2+ channels.
Next the authors attempted to activate the latent stem cells in vivo, using pilocarpine to invoke seizures, and thus hippocampal synaptic activity, in mice. More neurospheres were derived from the hippocampi of mice that had exhibited prolonged seizures than from those in which seizures occurred in short bursts. This effect could even be seen in the hippocampi of aged mice. However, even prolonged seizures did not result in the generation of large stem-cell-like neurospheres, suggesting that additional factors are required to activate the stem cell population in vivo.
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