Apr 22, 2002
Stem cells derived from adult hippocampus are similar to those from developing brains in their ability to develop into functional central nervous system neurons, researchers from the Salk Institute report.
Dr. Charles F. Stevens and associates in La Jolla, California, co-cultured the labeled progeny of stem cells isolated from the hippocampus of adult rats with primary neonatal hippocampal astrocytes and neurons, and then with adult astrocytes. As they report in the advance online publication of Nature Neuroscience for May, the location of the axonal growth-cone protein and a dendritic protein marker showed that the adult stem cells established appropriate neuronal polarity.
Furthermore, the cells expressed proteins--glutamate and one of its receptor subunits, as well as calcium/calmodulin-dependent protein kinase II--similar to those found in mature neurons.
Typical synaptic structures of the stem cells were associated with the dendrites, spines, and cell bodies. Synapses formed between stem cell neurons and primary neurons, as well as between stem cell neurons themselves.
Dr. Stevens and his associates were able to induce repetitive action potentials that were reversible by tetrodotoxin. They also observed spontaneous neurotransmitter release from synaptically connected neurons and spontaneous synaptic currents. The latter were mediated by glutamate or GABA, sometimes even in the same cell, demonstrating their ability to receive both excitatory and inhibitory inputs.
The stem cell-derived neurons exhibited lower efficacy of synapse formation and synaptic transmission compared with primary neonatal neurons. However, the addition of brain-derived neurotrophic factor to the culture medium increased the percentage of neurons showing excitatory spontaneous synaptic currents, as well as the amplitude and frequency of these currents.
"Up to now we've known that stem cells from brain tissue developed into cells that looked like neurons," Dr. Thomas Reh, a neurobiologist at the University of Washington School of Medicine in Seattle, told Reuters Health. "This is the first time that it's been shown they actually work like neurons, and that environmental factors could enhance their functional differentiation."
Dr. Reh noted that, in a companion paper, Dr. Stevens' team of investigators showed that new neurons would reach functional maturity in the adult hippocampus. "There they showed that, not only do adult-derived cells show a differentiated appearance, but they also fit into the neural circuit and receive synaptic input from other neurons," he said.
© 2002 Reuters Ltd