UM scientists focus on diseases attacking the brain

Scientists at the University of Montana are looking at the brain at the tiniest chemical level to learn about how diseases such as Alzheimer’s and stroke harm the memory, UM biochemist Rich Bridges told a Missoula audience Tuesday night.

By GINNY MERRIAM of the Missoulian

The techniques of MRI and PET scanning can show researchers where chemicals in the brain concentrate under certain conditions. The scientists and students in Bridges’ laboratory are looking at glutamates, which the brain uses to learn.

The best experiments, Bridges said, generate more questions than answers. Each answer leads to more what-ifs and buts.

"In science and in research, just when you think you have the upper hand, it slaps you in the face," he told about 50 people gathered for his talk in the Montana Neurosciences Institute Foundation public lecture series in the Broadway Building of St. Patrick Hospital.

Brain cells called neurons create electrical signals inside the cells. At the edge of a cell, the electrical signal changes to a chemical signal. That signal communicates to the next cell in the space between the cells. That’s the place where anything that gets in the brain can interfere with its communication. That intervening substance could be a harmful substance or a helpful drug, Bridges said.

Glutamate, one of the building blocks of protein, is one of the most prevalent signaling molecules in the brain. It activates five different kinds of receptors in neighboring cells. One of the most interesting is a receptor called NMDA. When scientists trace the NMDA with radioactive drugs to show where it goes in the brain, they find it in high levels in the hippocampus portion of the brain. That’s the portion that degenerates in Alzheimer’s disease patients.

Work done by scientists around the country has painted a picture of the brain learning at the cellular level, Bridges said, with the cells acting different after they’re bombarded with signals.

When scientists inject the brains of rats with drugs that block the NMDA receptors, the rats don’t learn and can’t remember where to go in a maze to find food, even though they’ve been there before.

That leads to the question: Could humans take a drug that would give us more NMDA receptors to enhance learning and memory?

But back in the lab, brain cells growing in culture die when they’re exposed to too much glutamate. Glutamate levels gone awry seems to be what causes the damage in stroke, Alzheimer’s disease, ALS (Lou Gehrig’s disease) and spinal cord injuries. Glutamates also play a role in the damage of Parkinson’s disease, Huntington’s disease and epilepsy.

Sure enough, in the lab, when a drug that blocks the NMDA receptors is injected into the brain, the brain is protected from the damage of excess glutamate.

So, Bridges said, "Can we come up with a drug that blocks this process?"

Clinical trials are going on now at St. Patrick Hospital, which is partners with UM in the Montana Neurosciences Institute. Just more than two weeks ago, the Food and Drug Administration approved a blocking drug tested elsewhere for use in end-stage Alzheimer’s disease.

Research going on in Missoula is very promising, Bridges said, and the partnership between the university and the hospital is an ideal one.

Bridges is a professor in the Department of Biomedical and Pharmaceutical Sciences in the School of Pharmacy and Allied Health Sciences. He’s the director of its National Institutes of Health Center of Biomedical Research Excellence in Structural and Functional Neuroscience.

Eight or nine years ago, the school drew about $250,000 in research money. Last year, it drew $10 million.

Missoula neurosurgeon Nick Chandler will give the next talk in the public lecture series. He will speak at 7 p.m. Dec. 2 in the Broadway Building about "Recent Advances in Brain Surgery."

Reporter Ginny Merriam can be reached at 523-5251 or at [email protected]

http://missoulian.com/articles/2003/11/21/news/mtregional/znews08.txt