Growth Factor Stimulation Leads To Increase In New Neurons In The Striatum And Cortex Of The Brain

October 27, 1997

NEW ORLEANS -- The number of new neurons in the striatum and cortex, key areas of the brain responsible for movement, vision and higher mental functions, can be increased in adult rats through stimulation with a growth factor, Emory University and Regeneron Pharmaceuticals, Inc. researchers report at this week's Society for Neuroscience meeting.

The researchers administered the brain-derived neutrotrophic growth factor (BDNF) to the right lateral ventricle of the brains of adult rats. Not only did they confirm their previous findings that the number of neurons was increased in the olfactory bulb of the brain, but also that the number of neurons in the striatum and outer brain, or cortex, increased significantly.

Contrary to a long-held belief that neurons cannot reproduce themselves, Marla Luskin, Ph.D., associate professor of cell biology at Emory University School of Medicine, and colleague Tanja Zigova previously demonstrated that the adult mammalian forebrain has a remarkable capacity to produce new neurons. They identified and isolated a population of virtually pure neuronal cells - cells that have the capacity to produce more neurons - in the anterior part of the brain?s subventricular zone (SVZa).

This population was unlike all other cell populations in the developing brain which contain a mixture of progenitor cells for neurons and glial cells. Dr. Luskin demonstrated that this region actively produces new neurons both in vivo and in tissue culture. These newly generated neurons were found to travel to the olfactory bulb in the forebrain. In recent work they were able to significantly increase neuronal production in the olfactory bulb of the SVZa by administering BDNF in the ventricles of adult rats.

In their latest work, the researchers have demonstrated that after BDNF is administered, neuronal production also increases in the proliferative layer of the subventricular zone (SVZ), the origin of neurons destined for the striatum and cortex. In order to track newly generated cells, they administered the cell proliferation marker BrdU along with the BDNF to label the cells generated during infusion of the brain with the growth factor.

They observed significantly more BrdU-labeled cells throughout the SVZ on the infused side of the brain compared to the contralateral side or in control animals. Numerous marked cells, many of which were neuronal cells, also were found in the parenchyma adjacent to the SVZ.

The finding that a mammalian brain can be stimulated to produce new neuronal cells in these particular parts of the brain raises new hope that someday these cells will be valuable in treating neurological diseases including Huntington's disease, Parkinson's disease, and Alzheimer's disease. If these cells differentiate into neurons they would synthesize neurotransmitters, or chemical messengers used by neurons, that are in short supply in a number of neurological diseases. Luskin and colleagues have shown that the neurons arising in the SVZa, for example, manufacture the neurotransmitter gamma-aminobutyric acid (or GABA) and tyrosine hydroxylase (TH), a key enzyme used during the synthesis of dopamine. Cells that use these neurotransmitters in the striatum die in two devastating neurological diseases: GABA-containing cells die in Huntington?s disese and TH-containing cells die leading to Parkinson's disease.

The researchers hope their findings may reveal new ways of producing large numbers of new neurons to replace diseased or damaged cells. Future studies will address the mode of action of BDNF - whether it directs cells to become neurons or whether it prevents the death of neurons, as well as whether the population of new neurons is sustained if the infusion of BDNF is terminated.

Emory University Health Sciences Center

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