Isabel Kimura, and David M. Tuller.
The researchers compared this novel design to existing methods used for studying the mechanisms by which dopamine interferes with learning and memory in the hippocampus. By focusing solely on the effects of the dopamine-based drug on rats, the team found that the treatment had beneficial effects on learning and memory.
The research was conducted in a large laboratory and required several months to complete, which made it relatively rapid, said Tuller, a professor of neuroscience at Tufts University who is director of the Center for the Study of Dopamine Transmission.
“For a drug like rituximab to show promise for this kind of study, it is not like a drug that comes for a study and gets published in a very clear, well-publicized article,” said Tuller. “It needs several years of experimentation.”
In the new study, the researchers studied the effects of rituximab on rats with a history of Alzheimer’s disease that had already been treated with drugs that targeted the same receptors in the hippocampus, as is typical of current Alzheimer’s drugs. Rats treated with the new treatment showed improved learning and memory, and behavioral symptoms such as reduced anxiety, but not improvement in learning or memory.
“One of our biggest challenges was to isolate rituximab from other known dopamine agonists,” said Tuller. “We used a combination of antibodies and ritonavir, a monoclonal antibody that specifically targeted the human receptor [DAT]. Because we used the same type of antibodies, we could be sure that each was specifically working on a specific receptor.”
The team also used the antibody cocktail to determine which type of signaling, or receptor, was responsible for improving learning. Ultimately, they determined that the serotonin receptor was to blame.
Although human brain cells respond to a wide variety of drugs, the researchers demonstrated that the changes in learning and memory had only significant effects in the hippocampus, which has been implicated in regulating complex behaviors and memory processing.
“The work in this group represents one of the most exciting developments in neurodegenerative neurosciences over the last year or so,” said Paul Armentano, an instructor of psychiatry and behavioral sciences at NYU who was not involved in the research. “This group demonstrated that by applying the same molecular approach to studying specific signaling events in humans, they have successfully identified and