November 2, 2010

How Neurons Are Born, Maintained May Answer Critical Questions

Once, scientists and doctors thought we were born with a certain number of neurons and those had to last us throughout our lifespan.

Today, neurologists know that new neurons can be produced in adulthood. These adult hippocampal newborn neurons arise in the hippocampus, an area of the brain responsible for learning and memory. Understanding how these neurons live and die could answer questions about diseases that affect learning and memory said Dr. Amanda Sierra Saavedra, a postdoctoral associate in pediatrics-neurology at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.

In a report in the journal Cell Stem Cell, Saavedra and her mentor, Dr. Mirjana Maletic-Savatic, an assistant professor of pediatrics-neurology, show that within one to four days, the newborn cells reach a critical stage.

At that point, many of them undergo programmed cell death (apoptosis) and are cleared rapidly by phagocytosis (a process of engulfment) by microglia (small cells in brain). These two processes "“ death and removal "“ are intrinsically coupled.
Following the cycle

Sierra Saavedra and her team labeled and follow each new neuron using a chemical called BrdU (Bromodeoxyuridine). BrdU can be incorporated into the newly synthesized DNA of dividing cells, enabling researchers to follow their life cycle.

"We found two critical periods when the newborn cells underwent apoptosis usually one to four days after they were 'born,'" said Sierra Saavedra. "This is much earlier than what we had first thought. We were completely puzzled to learn that many cells die almost immediately after they are born."

As researchers followed these cells, they soon learned that the "clearing up", or phagocytosis, began immediately following cell death. Microglia cells, which make up the immune defense system of the brain, engulf the dead cells, destroying them and leaving behind no trace.

"This process happens quickly, efficiently, and without any interference, indicating that the microglia play an important role in maintaining the proper functions of the neurogenic process," Sierra Saavedra said. "If this is interrupted by genetic, environmental, toxic, or immunologic defaults or any other reason, then we believe that certain diseases and disorders might appear."

In the future, the scientists hope to harness these newborn cells in order to treat disorders related to the hippocampus, she said.

This work was supported by the National Institute of Neurological Disorders and Stroke; the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Intellectual and Developmental Disabilities Research Center, and the Farish Foundation.

Others who contributed to this research include Juan M. Encinas, department of pediatrics at BCM and Cold Spring Harbor Laboratory; Juan J.P. Deudero, department of pediatrics at BCM; Jessica H. Chancey and Linda S. Overstreet-Wadiche, both of the University of Alabama; Grigori Enikolopov of Cold Spring Harbor Laboratory; and Stella E. Tsirka of Stony Brook University in New York.


On the Net: