Although thousands of new brain cells called neurons are produced each day in adults brains, only a small percentage of them survive. The cells that die are consumed by scavenger cells called phagocytes. Researchers have not completely understood how this process works, which phagocytes are unique to the brain and how the removal of dead neurons influences the creation of new neurons, until now.

During adulthood neurogenesis, or the development of new neurons, largely ceases in most areas of the brain. Yet, in two areas of the brain there is a strong indication that substantial numbers of new neurons are naturally created (in the hippocampus, an area of the brain involved in memory forming, organizing and storing, and the olfactory bulb, involved in the perception of odors).

UVA Health System investigators have made an important discovery in understanding this complex process, which may help scientists create new therapies to promote neurogenesis in the adult brain and re-establish its function in patients suffering from depression, post-traumatic stress disorder, and other mental disorders, in which adult neurogenesis is impaired.

Published online July 31st, 2011, the discoveries were led by two UVA researchers – Jonathan Kipnis, PhD, associate professor of neuroscience, and Kodi S. Ravichandran, PhD, chair of the UVA Department of Microbiology and director of the UVA Center for Cell Clearance can be found in the journal Nature Cell Biology.

The first author on this report was Zhenjie Lu, PhD, who was active in combining the methodologies in the Kipnis lab (which concentrates on basic mechanisms underlying neurological disorders) and the Ravichandran lab (which concentrates on cell clearance) to address adult neurogenesis through a combination of in vivo investigations in normal and genetically altered mice, and ex vivo investigations using neuronal cultures.

UVA scientists found that certain types of progenitor cells, called the doublecortin (DCX) – positive neuronal progenitors (or “newborn neurons”), serve a double role in the regulation of creation and elimination of new neurons. Replenishing special cells and maintaining blood, skin and intestinal tissues, progenitor cells usually act as a repair system for the body. This new finding highlights the capability of these cells to clean each other out, which ultimately benefits the regeneration process.

Kipnis explains:

“Our study provides the first evidence that DCX+ cells, in addition to serving their function as neuronal precursors in the brain, also function as phagocytes (scavenger cells) by clearing out their dead brethren – and that this process is required to maintain continuous generation of new neurons in the brain.”

Ravichandran says:

“These findings raise the possibility that this newly discovered process could be manipulated to rejuvenate the brain by regulating the addition of new neurons.”

This discovery may also shed new light on our understanding of how the process of adult neurogenesis is regulated in the healthy brain, and in turn give insights on diseased brains, where adult neurogenesis is severely impaired, Kipnis adds.

Kevin Lee, PhD, chair of the Department of Neuroscience and professor of neurological surgery says:

“The birth and death of new neurons in the adult brain have been implicated in ongoing learning and memory.

The findings by Kipnis, Ravichandran, Lu and associates are fascinating, because they describe a novel process regulating the production and removal of adult-born neurons. This represents an important step toward identifying mechanisms that might be manipulated to control the number of new neurons in the adult brain. Regulating new adult neurons in this manner could open a novel avenue for modifying basic cognitive functions, including learning.”

Written by Grace Rattue