Emory University researchers have demonstrated that several regions of the adult rat brain have the capacity to acquire new neurons following the introduction of a growth factor into the brain’s lateral ventricle, located in the depths of the cerebral cortex. The study is the first to show the presence of numerous new neurons in certain regions of the brain where they previously have not been found, and suggests that the adult brain may be able to replace neurons lost due to injury or disease. The results were published in the September 1 issue of the Journal of Neuroscience.
The research team, headed by Emory Professor of Cell Biology Marla Luskin, Ph.D., also included Emory cell biology fellow Viorica Pencea, M.D., Kimberly Bingaman, M.D. and Stanley Wiegand, Ph.D., of Regeneron Pharmaceuticals, Inc.
Although the majority of neurons in the forebrain of mammals are formed prenatally, scientists have learned over the past few years that certain areas of the adult brain can produce new neurons, including the hippocampus and the subventricular zone (a cell layer surrounding the lateral ventricles of the forebrain).
The Emory scientists administered the growth factor BDNF (brain-derived neurotrophic growth factor) into the lateral ventricle of the brains of adult rats for approximately two weeks, and waited another two weeks before they examined the brains for the presence of new cells. They detected newly generated neurons in several forebrain structures, including in the parenchyma (gray matter) of the striatum, septum, thalamus and hypothalamus — areas that serve a multitude of cognitive and vital neurological functions. The newborn cells were identified by infusing the brain with the cell proliferation marker BrdU, which serves as a permanent label for newborn cells, in conjunction with the BDNF. Until this study was done, neurogenesis (the production of neurons) had not been demonstrated in the thalamus and hypothalamus during postnatal life, and in only very limited numbers in the septum and striatum.
Earlier studies had shown that most new cells in the adult brain originate in the subventricular zone surrounding the lateral ventricles. Furthermore, Dr. Luskin’s experiments previously showed that a specialized region of the postnatal subventricular zone contains progenitor cells whose progeny (daughter cells) migrate along a pathway known as the rostral migratory stream to the olfactory bulb. Dr. Luskin and colleagues demonstrated that the special region of the subventricular zone and the rostral migratory stream contain a unique population of dividing neurons (neuronal progenitor cells). Everywhere else in the brain, neurons are post-mitotic cells (unable to divide). Dr. Luskin’s previous experiments demonstrate that BDNF infusion leads to an immense increase in the numbers of new neurons in the rostral migratory stream and olfactory bulb, a portion of the brain involved in the processing of smells..
"These studies led us to investigate whether infusing BDNF could influence the proliferation and/or survival of neurons in other regions of the adult forebrain as well," Dr. Luskin said. "The number of new neurons we found in regions such as the striatum and hypothalamus suggests to us that the adult forebrain has a more profound capacity to produce new neurons than previously has been recognized," she said.
The researchers hope their findings may reveal novel ways of producing large numbers of new neurons to replace diseased or damaged cells in localized parts of the brain. Future studies will continue to address the mode of action of BDNF, whether the population of new neurons is sustained long after the infusion of BDNF is terminated and whether cells within the gray matter parenchyma can divide when exposed to BDNF, as the studies suggest.
The research was supported by grants from the National Institute of Deafness and Other Communicative Disorders of the National Institutes of Health (NIH).
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