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Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons

Abstract

Neural stem cells are present both in the developing nervous system and in the adult nervous system of all mammals, including humans. Little is known, however, about the extent to which stem cells in adults can give rise to new neurons. We used immunocytochemistry, electron microscopy, fluorescence microscopy (FM imaging) and electrophysiology to demonstrate that progeny of adult rat neural stem cells, when co-cultured with primary neurons and astrocytes from neonatal hippocampus, develop into electrically active neurons and integrate into neuronal networks with functional synaptic transmission. We also found that functional neurogenesis from adult stem cells is possible in co-culture with astrocytes from neonatal and adult hippocampus. These studies show that neural stem cells derived from adult tissues, like those derived from embryonic tissues, retain the potential to differentiate into functional neurons with essential properties of mature CNS neurons.

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Figure 1: Maturation and synapse formation by neural progeny of adult stem cells.
Figure 2: Electrical properties of neural progeny of adult stem cells.
Figure 3: Summary of physiological properties of neural progeny of adult stem cells.
Figure 4: Co-culture of adult stem cells with primary astrocytes from neonatal hippocampus.
Figure 5: Functional maturation of neural progeny of adult stem cells in co-culture with primary astrocytes from neonatal hippocampus.
Figure 6: Co-culture of adult stem cells with primary astrocytes derived from adult hippocampus.

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Acknowledgements

We would like to thank R. Jacobs for help on EM studies, Y. Zhu for FM4-64 studies and M. Gage and J. Sullivan for comments. This work is supported by the Howard Hughes Medical Institute, National Institutes of Health, Christopher Reeve Paralysis Foundation, National Institues of Aging, the Michael J. Fox Foundation, Project ALS and the Lookout Fund. C. F. S. is an investigator and H-j. S. is a postdoctoral associate of the Howard Hughes Medical Institute.

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Correspondence to Charles F. Stevens or Fred H. Gage.

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Song, Hj., Stevens, C. & Gage, F. Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat Neurosci 5, 438–445 (2002). https://doi.org/10.1038/nn844

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