by: Elianne Ortiz, Hanszen ’11
Contrary to popular belief, the number of neurons in the human body is not fixed at birth. Through a process called neurogenesis, stem cells continue to differentiate into neurons throughout adulthood at specific regions of the brain — namely the olfactory bulb and hippocampus. The olfactory bulb is responsible for smell, while the hippocampus plays a role in long-term memory. Neurons in the hippocampus proliferate with enough mental and physical exercise, but their purpose had long remained unknown. A recent study by a team of investigators at the Salk Institute in La Jolla, California, finally shows some promise of shedding light on this mystery. They created a method to genetically engineer mice to turn off the processes that are responsible for neurogenesis.
In an earlier study, researchers Ronald M. Evans, Ph.D., and Fred H. Gage, Ph.D., had previously discovered a crucial mechanism that kept adult neuronal stem cells in an undifferentiated, proliferative state.3,4 After learning more about its specific function, Dr. Chun-Li Zhang, postdoctoral fellow at the Salk Institute, was able to turn off this mechanism in mice. This procedure effectively suppressed neurogenesis in the hippocampus, allowing the scientists to identify how newborn neurons affect brain functions.
The altered mice were then put through a series of behavioral and cognitive tests, one of which yielded results that conflicted with those of the control population. The Morris water maze is used to study the formation of learning strategies and spatial memories. Mice placed in deep water try to find a submerged platform with the help of cues marked along the walls of the pool. As the test was repeated, a normal mouse remembered the cues in order to locate the platform with relative ease. On the contrary, the mice that were genetically engineered to lack neurogenesis showed slower improvement. These mice experienced significant difficulty in finding the submerged platform, and their performance declined as the task was made more demanding. Although these mice were slower at forming efficient strategies, their behavior was very similar to that of the control mice by the end of the experiment. “It’s not that they didn’t learn, they were just slower at learning the task and didn’t retain as much as their normal counterparts,” Zhang said in an interview with Science Daily.1
This study suggests that neurogenesis has a specific role in the long-term storage of spatial memory, the part of memory responsible for processing and recording information from the environment. “Whatever these new neurons are doing it is not controlling whether or not these animals learn. But these new cells are regulating the efficiency and the strategy that they use to solve the problem,” Gage explained to Science Daily.1
In previous studies, Gage and his team were able to show how certain activities trigger neurogenesis. For instance, increased mental and physical exercise led to an increased amount of stem cells differentiating into neurons.3 Many of these neurons did not survive, although continued stimulation increased the number that did. Zhang’s water maze study now provides an important tool for others to study the effects of decreased neurogenesis. Previous attempts using radiation and mitotic inhibitors shut down not just neurogenesis but all cell division, and thus led to contradictory results.
The significance of Zhang’s research on adult neurogenesis is well founded. There are over 5 million people in the U.S who suffer from Alzheimer’s disease and other neurodegenerative disorders. Studies such as these give hopes that there may be a way to influence memory function by stimulating neurogenesis with therapeutic drugs. When perfected, these methods will allow a debilitating disease, such as Alzheimer’s, to be cured with a drug, followed by physical and mental stimulation. Many neurodegenerative disorders have no cure, and symptoms can only be alleviated for a short period of time before damage becomes severe. These groundbreaking studies have the potential to save millions from the trauma of memory deterioration.
References
1. Science Daily. http://www.sciencedaily.com/releases/2008/01/080130150525.htm. (accessed Feb 26, 2008).
2. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, Gage FH, Evans RM. Expression and function of orphan nuclear receptor TLX in adult neural stem cell. Nature. 1 Jan 2004.
3. Tashiro A, Makino H, Gage FH. Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. The Journal of Neuroscience. 21 Mar 2007.
4. Zhang CL, Zou Y, He W, Gage FH, Evans RM. A role for adult TLX-positive neural stem cells in learning and behaviour. Nature. 21 Feb 2008.