New compound improves cognitive decline, symptoms of Alzheimer's disease in rodents

January 12, 2010

A fast-acting compound that appears to improve cognitive function impairments in mice similar to those found in patients with progressive Alzheimer's disease has been identified by scientists at Wake Forest University School of Medicine and the Vanderbilt University Medical Center Program in Drug Discovery. Researchers hope to one day replicate the result in humans.

The compound - benzylquinolone carboxylic acid (BQCA) - has also been shown in previous rodent studies to lessen the occurrence and severity of the behavioral disturbances often symptomatic of Alzheimer's, such as hallucinations, delusions, paranoia and outbursts.

"That makes this compound somewhat novel," said Michelle M. Nicolle, Ph.D., an associate professor of at Wake Forest and co-researcher on the study, published recently in the . "We wanted to see if this very specific acting compound was able to change the way the brain works and whether or not it improved memory in our 'Alzheimer's mice,' which are experiencing progressive much like a person with Alzheimer's does."

Other attempts to identify such a specific treatment for Alzheimer's have failed, according to Nicolle.

"Current treatments only treat the symptoms while the underlying disease is still progressing," she said, "so recent research efforts are focusing on stopping disease progression instead of symptomatic treatment."

The researchers' findings suggest that the compound could alter the progression of disease in mice and, ultimately, hold importance for humans, as well.

BQCA activates a specific neurotransmitter receptor in the brain called the M1 muscarinic acetylcholine receptor. M1 have been the focus of research into treatment of Alzheimer's disease because they affect the part of the brain that stimulates the memory and learning functions the disease inhibits. Until now, scientists have not found a treatment selective enough to activate the receptors without producing side effects such as nausea, vomiting and increased frequency of urination.

But in this study, Nicolle said, researchers found that BQCA boosted the weak signals of the M1 receptors in a mouse model of Alzheimer's disease.

"In Alzheimer's disease, the chemical signals - the little bits of information that are talking to each other in the brain - are reduced, so you can't do the tasks very well," Nicolle said. "BQCA is only boosting an existing signal, so it's really specific in its action."

BQCA also seemed to inhibit production of amyloid beta, one of the markers of Alzheimer's disease in the brain - perhaps key to the compound's potential for slowing the progression of the disease.

Moreover, the compound works quickly, Nicolle explained. After just one administration of BQCA one hour before behavioral testing, mice were able to learn new ways to do tasks - in this case, finding a piece of hidden chip in one of two small flower pots that looked the same but smelled different. One of the pots was made to smell like lemon, indicating the location of a food reward, namely the peanut butter chip. The other pot smelled like clove, a smell that if followed, would lead the mouse to a pot with no food reward. All mice learned to locate the peanut butter chip in the pot that smelled like lemon.

However, when the odor stimuli were switched, making clove the indicator of the peanut butter and lemon the indicator of no reward, the BQCA-treated "Alzheimer's mice" were able to forget the old rule and quickly learn the new rule to locate the chip in the clove-scented pot. The untreated Alzheimer's mice had difficulty learning the new rule and persisted in looking for the chip in the lemon-scented pot - a characteristic of impaired cognitive function known as "perseveration."

Tasks that require the replacement of old rules with new rules are categorized under the broad umbrella of cognition called "executive function" in humans. Examples of executive function such as planning, multitasking and activities of daily living, like cooking and getting dressed, are all capabilities that slip away as Alzheimer's disease progresses.

"In older people and in Alzheimer's disease patients, we call it flexible learning," Nicolle said. "They learn one rule, and they don't want to change the rule to get to the end goal."

Treatment with BQCA in mice allowed a previously learned rule to be replaced with a new one.

Because of the early indications that the compound could treat the behavioral symptoms associated with Alzheimer's, the researchers also believe BQCA could be targeted for treatment of schizophrenia. However, the compound will need further testing in the laboratory before it is ready for clinical trials with human participants.

Related Stories

Recommended for you

Researchers find monkey brain structure that decides if viewed objects are new or unidentified

August 18, 2017
A team of researchers working at the University of Tokyo School of Medicine has found what they believe is the part of the monkey brain that decides if something that is being viewed is recognizable. In their paper published ...

Artificial neural networks decode brain activity during performed and imagined movements

August 18, 2017
Artificial intelligence has far outpaced human intelligence in certain tasks. Several groups from the Freiburg excellence cluster BrainLinks-BrainTools led by neuroscientist private lecturer Dr. Tonio Ball are showing how ...

How whip-like cell appendages promote bodily fluid flow

August 18, 2017
Researchers at Nagoya University have identified a molecule that enables cell appendages called cilia to beat in a coordinated way to drive the flow of fluid around the brain; this prevents the accumulation of this fluid, ...

Study of nervous system cells can help to understand degenerative diseases

August 18, 2017
The results of a new study show that many of the genes expressed by microglia differ between humans and mice, which are frequently used as animal models in research on Alzheimer's disease and other neurodegenerative disorders.

Researchers make surprising discovery about how neurons talk to each other

August 17, 2017
Researchers at the University of Pittsburgh have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge ...

Neurons involved in learning, memory preservation less stable, more flexible than once thought

August 17, 2017
The human brain has a region of cells responsible for linking sensory cues to actions and behaviors and cataloging the link as a memory. Cells that form these links have been deemed highly stable and fixed.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.