HOUSTON, March 12, 2002 - Can't remember where you put your keys, or how to retrieve your voicemail? Your brain's cleaning crew may be asleep on the job. Molecular "brooms" that whisk away excess amounts of the chemical glutamate in the brain may play a key role in learning and memory formation, suggest recent animal studies by scientists at the University of Houston.
In the brain, several chemicals called neurotransmitters carry messages in the spaces connecting one nerve cell, or neuron, to the next, allowing the brain to function properly. Scientists believe that the strengthening of these connections by the neurotransmitter glutamate - a process called long-term potentiation - is one mechanism responsible for the storage of some memories.
Now, for the first time, researchers at the University of Houston have determined that levels of transport molecules for glutamate - chemicals that latch on to and "sweep away" glutamate - increase during learning, suggesting that this molecular cleaning crew has an important role in the process.
In experiments with rats, the UH team found that glutamate transport molecules increased by more than 100 percent in a region of the brain called the hippocampus 30 minutes after the onset of long-term potentiation - the memory-forming process.
"These results suggest that the regulation of glutamate uptake by the transport molecules may be important for maintaining the strength of connections among the neurons in the area of the brain associated with memory," says UH biochemist Arnold Eskin, one of the authors of a study appearing in the February issue of Nature Neuroscience.
"We imagine that the way the nervous system stores information in rats is similar to the way it might work in humans," he says. "Maybe there are people who can't learn as well because their transporters are out of whack, or have memory problems because there are deficiencies in their glutamate transporters. Before we did these studies no one was even asking these questions. Now we have a fundamental reason to investigate this mechanism further.
"We knew that glutamate is involved in learning, but our study is the first to investigate the role of glutamate transporters and glutamate uptake in the learning and memory formation process," Eskin says. In the rat studies, which have been successfully reproduced, Eskin and his research team first trained the animals repeatedly over a period of time, which produced a change in behavior in the rats. They then examined the transporters in the animals' hippocampus region.
"The way you know that the animal remembers what you've done is because its behavior has changed as a result of experience, which is the definition of learning," Eskin says. "Its nervous system remembers that event, and we know there have been changes in the system because the animal gives us a different behavior."
UH doctoral student Jonanthan Levenson performed most of the research, assisted by UH undergraduate student Lorna Kategaya and Baylor College of Medicine researchers Edwin Weeber, Joel Selcher and J. David Sweatt. All are co-authors on the study. Eskin says the job of glutamate transporters in the brain is two-fold.
"Clearing away neurotransmitters allows the next batch of chemical messengers to deliver a 'clean' signal between neurons," he says. "Also, in the case of glutamate, which desensitizes its receptors and kills nerve cells if too much hangs around too long, transport molecules are essential to maintaining effective transmission and a non-toxic environment in the brain."
Other studies have suggested that deficiencies in glutamate transporters may be responsible for neuron damage and death associated with neurodegenerative diseases such as amyotrophic lateral sclerosis, or Lou Gherig's disease.
Eskin's research is funded by the National Institutes of Health.
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