Neural stem cells, it turns out, are found throughout the brain, although neurogenesis, or the emergence of new neurons, generally takes place in just a few brain areas. Notable areas containing NSCs include the dentate gyrus of the hippocampus and the subventricular zone. Neurogenesis in these areas is believed to underlie important brain functions, including adaptation to the environment and memory.
NSCs are mutipotent (or pluripotent) rather than totipotent; that is, they can become several kinds of specialized adult cells, but only a few. (In contrast, embryonic stem cells can develop into any kind of cell in the body; they?re totipotent.)
Neural stem cells are found in tissue that lines the brain?s lateral ventricles, the hollow areas of the brain containing cerebral spinal fluid.
Usually, when these neural stem cells develop, they become glia. Glia are very common cells in the brain ? in fact, many times more common than neurons.
However, these same neural stem cells can become neurons instead, under the right conditions. Recent research shows they can be prompted to develop in significant part as new neurons, rather than glia, when exposed to the right growth or trophic factors. Trophic factors stimulate and guide growing neurons to their target locations, and help maintain new nerve cell connections.
|Precursor neural cells grow in a lab dish, generating mature neurons (red) and glial cells (green) (Courtesy Su-Chun Zhang, University of Wisconsin-Madison).|
Steven Goldman and his colleagues at Cornell University Medical College, Regeneron Pharmaceuticals, and the University of Rochester attempted to exploit these neural stem cells to achieve an innovative kind of brain repair (see abstract below). Using a technique known as viral gene therapy, they inserted the genes that produce two trophic factors, BDNF and noggin, into two different adenoviruses (viruses like the common cold). The adenoviruses were then injected into rat brain ventricles. From there, the viruses could infect cells in the ventricle walls, with the viral genes poised to replicate. Inside the brain cells, the adenoviruses began producing the two trophic factors using the cells? machinery.
Earlier research had shown that the protein BDNF [brain-derived neurotrophic factor] is needed to promote the emergence and survival of new neurons. Other studies had shown that the protein noggin inhibits the development of glial cells. The idea of Goldman?s team was to increase these two trophic factors (normally present in the brain at lower levels), to discourage the development of glial cells through the presence of noggin, and to encourage the development of neurons through the presence of BDNF at the same time.
The exciting finding of this research was that, not only did many new neurons develop, they integrated with the nearby brain area, the striatum, and they developed specifically into medium spiny neurons in the striatum. These are the neurons and the brain region most affected in Huntington?s disease. Moreover, the newly developed neurons established exactly the types of connections that medium spiny neurons normally form in the human brain, and they began functioning in ways like normal medium spiny neurons, including in the neurotransmitter they use (the neurotransmitter GABA).
These findings may provide great benefits for people with Huntington?s down the pike. However, to realize their promise will require additional research steps and clinical trials. Dr. Goldman?s lab at the University of Rochester is now testing the experimental protocol described above specifically in R6/2 model Huntington?s mice. Beyond these fascinating horizons, gene therapy covers still more ground than Huntington?s alone, and developments elsewhere in this field may also help accelerate HD therapies.
The abstract of the research paper by Goldman and colleagues follows. The full article can be found at http://www.jneurosci.org/cgi/content/full/24/9/2133 .
(For more on gene therapy, see http://en.wikipedia.org/wiki/Gene_therapy. For more on BDNF?s supporting the growth of new neurons and on the roles of BDNF in Huntington?s disease, see .../research/brain/updates/1202bdnf.php and .../research/drugs-supps/updates/1206neurotrophins.php. To increase BDNF levels using safe, available measures, see .../see/drugs/bdnfdrugs.htm, .../treatment-care/care/hdltriad/exercise/updates/1243bdnf.php, and .../TreatmentNow/updates/0085-SSRItreatment.php.)