April 8, 2002

very day your brain is bombarded by insults - not the kind that bruise feelings, but physical and biological assaults on your brain. The brain's natural ability to recover from these minor pathological events is at the heart of Ben Bahr's research, and has led to two significant discoveries relating to Alzheimer's disease.

For some time, scientists have speculated that the brain has a self-repair mechanism. This mechanism is the reason why people do not suffer significant brain damage while sitting in traffic inhaling toxic fumes from a bus, or after a slight knock in the head from a basketball, or because of several breathless moments after running up a couple flights of stairs. We encounter all kinds of insults all day long, and without the brain's ability to fight back, any of those things and many more can cause a small change in brain chemistry and result in permanent damage.

Bahr's research shows that the brain possesses not one, but two separate and distinct cellular self-repair systems. One kicks into action in response to stroke-induced damage, and the other during neurodegenerative disorders like Alzheimer's disease. He also discovered a method for tapping into and enhancing one of the self-repair systems, that has led to a patent application.

"What we are looking at is a new way to treat Alzheimer's disease," says Bahr, an associate professor of pharmaceutical science and the Neurosciences Program at Storrs.

He arrived at UConn in 1998, after working with some of the top scientists studying memory mechanisms at the Center for the Neurobiology of Learning and Memory at the University of California-Irvine.

"By reproducing Alzheimer-type events in brain tissue living in a dish, we can follow the pathogenic process long before the neurons die, and then we can pinpoint the problem and target the therapy," he says.

The human brain consists of about 100 billion neurons - or nerve cells - which communicate, or signal one another, through an electrochemical process. Information from one neuron flows to another neuron across a tiny gap called a synapse. But in Alzheimer's patients, neurons are not allowed to communicate properly, because plaque deposits have reduced the number of synapses and tangles of a protein called tau have deposited inside neurons.

Contributing to these events are lysosomes - tiny bags of enzymes that act as a garbage disposal for neurons by processing and recycling proteins and carbohydrates - which have become disrupted. This disruption occurs during the very early stages of Alzheimer's disease and it all happens before the cells actually die.

Bahr's goal is to get to the cell before it dies, and tap into self-repair machinery to promote survival. He and his research team are focusing on potential therapeutics that act on survival signaling pathways.

In describing how survival signals work, Bahr compares them to "a fire station bell signaling everybody in the firehouse to go out and protect homes near a brushfire." In the brain, specific signals wake up growth stimulation factors, which go out and protect cells from irreversible damage. Bahr is identifying and discriminating between cellular signals that point nerve cells in the direction of disease and those that lead cells toward recovery.

Since it is impossible to conduct this type of research on a living human brain, Bahr developed a method for keeping slices of rat brain alive, while keeping the same electrical connections intact that are found in the human brain. Using this model, lysosomes were treated with inhibitors that target digestive enzymes of the lysosomes. This treatment created the protein deposits and synapse loss found in human Alzheimer's brains.

Bahr discovered that the internal repair system activated during stroke was not triggered during a lysosomal disturbance. Instead, he found a pronounced increase in the digestive enzymes used by lysosomes to process accumulated protein deposits inside neurons.

The next step was to find a way to bolster the enzymatic response to augment the brain's defense system. Using a memory-enhancing drug called Lypex, Bahr found that, in fact, the enzymatic response increased.

"Not only does our work indicate that the Alzheimer's brain is constantly trying to repair itself, it explains the long battle patients often endure, as the brain mounts its own defense against the disease," says Bahr who has spent 16 years researching the brain's memory and thought processing mechanisms. His research on neurodegeneration and neuroprotection has brought in nearly $800,000 in funding from the U.S. Army, the National Institutes of Health and several pharmaceutical companies.

Last year, Bahr was granted tenure - proudly accomplished in just three years at UConn. Last month, two of his papers were published in the Journal of Neuroscience Research and in Experimental Neurology. And Bahr is looking forward to July, when he will present his research findings at the bi-annual International Conference on Alzheimer's Disease in Stockholm.