16 Apr 2002

Ever since adult neuronal stem cells were shown to exist, those interested in neurodegenerative diseases have dreamt of using them for therapies. To this end, however, it must be shown that these precursors can actually differentiate into neurons that can integrate into an existing, complex neural network. Researchers in Fred Gage's lab at the Salk Institute, La Jolla, California, recently demonstrated that (see ARF news story). Now in an advance online publication in today's Nature Neuroscience, Hong-jun Song and Charles Stevens, together with Gage, extend those observations to neurons cultured in vitro from adult neuronal stem cells.

The authors used their previously described technique to induce stable expression of green fluorescent protein in neural stem cells from adult rats. This allowed them to follow the development of those cells in a variety of environments. When grown in culture with neonatal hippocampal neurons and astrocytes, for example, stem cell progeny had much longer neurites with more extensive branching than when stem cells were allowed to differentiate on the commonly used laminin substrate. Progeny also made extensive synaptic junctions and were electrically active; they could fire action potentials and receive both excitatory and inhibitory inputs. Similar results were obtained when the stem cells were cultured with astrocytes alone, either neonatal or adult.

In general, the stem cell progeny exhibited spontaneous synaptic currents that were less frequent and not as robust as those produced by neonatal neurons. However, the quality of these spontaneous currents, general indicators of neuronal fitness, could be increased by addition of brain-derived neurotrophic factor.—Tom Fagan

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