USC Groups Attend Neuroscience Meeting

Estrogen Plays Both Sides on Alzheimer’s

Hormone replacement therapy can worsen Alzheimer’s disease in older women but may prevent or delay the onset of the illness if started early, said Roberta Diaz Brinton, professor of molecular pharmacology and toxicology in the USC School of Pharmacy.

One of four panelists at a symposium on “The Aging Female Brain” at the 2006 annual meeting of the Society for Neuroscience, Brinton is scheduled to present findings from her latest study, published online from the journal Endocrinology.

Brinton’s research group set out to understand why HRT raises the risk of Alzheimer’s for women 65 and older, as determined by recent large clinical trials.

In the process, the USC researchers found that HRT may lower Alzheimer’s risk by as much as 50 percent in younger women.

“Essentially, they’re being treated in a prevention mode,” Brinton said. “If the [brain] cells are healthy, estrogen essentially promotes their survival.

In unhealthy cells, cells that are degenerating, it’s not great. It actually exacerbates the degenerative process.”

Brinton added that HRT, when started early, appears to lower the risk of many other degenerative diseases.

“It’s not that you don’t age,” she said. “You just age better.”

To exploit estrogen’s apparent protective mechanisms while minimizing its risks, Brinton’s group is attempting to develop “brain-selective estrogens” that would benefit neural networks without activating cancer-related sites in the breast or uterus.

Also at the 2006 SFN annual meeting, Brinton is scheduled to become only the fourth recipient of the society’s Science Educator Award, in recognition of her leadership in USC’s STAR program, a neighborhood outreach effort that reaches nearly 2,000 middle and high school students every year and brings many of them into the university’s laboratories for hands-on internships (www.usc.edu/hsc/USCSTAR).

A “very excited and very grateful” Brinton thanked USC’s Good Neighbors program, which she said “has supported us at every step of the way.”

Chicken-or-Egg Question in ALS Treatment

What goes first in the wasting disease known as amyotrophic lateral sclerosis: the muscles or the neurons that control them?

Most researchers have assumed that the neurons die off, starting the process of muscle wasting. But the story may not be so simple, according to a study by Chien-Ping Ko and colleagues in USC College.

Ko’s group crossbred mice genetically predisposed to ALS with mice lacking myostatin, an “anti-growth” factor for muscle development. Knocking out the myostatin gene increases muscle mass two- to three-fold, creating super-muscular mice.

When these super-mice contracted ALS, they maintained strong muscles and normal body weight almost until the end, the study reports. In addition, their motor performance remained nearly normal, while control mice with ALS became severely impaired. Two of the female super-mice with ALS also lived 20 percent longer than expected.

More surprisingly, the super-mice also retained 38 percent more motor control neurons, or motoneurons, through the midpoint of their illness. The increased muscle mass appears to start a feedback mechanism that keeps the spinal cord healthier.

“These results indicate that myostatin deletion can slow weight loss, muscle wasting and motoneuron death as well as improve motor performance and life span [females only],” the study concluded.

Anti-myostatin therapy also may help human ALS patients, Ko suggested.

“At the very least, it can improve the quality of life,” he said, adding that such therapy would be relatively easy. “You can enlarge skeletal muscle in a way that is less invasive to patients.”

Ko’s collaborators on the study were Yoshie Sugiura (a former research assistant professor at USC) and graduate students Sonia Ming-Yi Lin and Young-eun Yoo. The group is preparing its results for publication.

In a related presentation, Sugiura described the potential of testoterone therapy for improved motor performance in ALS mice.

And in a presentation on muscle improvements for patients with Parkinson’s disease, a group led by Beth Ellen Fisher of the Department of Biokinesiology & Physical Therapy in the USC School of Dentistry, found that high intensity exercise not only improves motor performance but also appears to promote beneficial brain changes (neuroplasticity) in the motor cortex.

“If humans with Parkinson’s disease are subject to neuroplasticity and behavioral recovery through high-intensity exercise, it is possible that exercise interventions may be designed to delay or reverse disease progression,” Fisher’s group concluded.

Do the Profane Make Profound Music?

“I am a vulgar man. But I assure you, my music is not,” says Mozart’s character in the movie “Amadeus.”

No one doubts the second part of that statement, but the first remains controversial. Some have suggested that Mozart suffered from Tourette’s Syndrome, characterized by verbal and/or motor “tic” outbursts.

The Mozart-had-Tourette’s camp may be right, according to a study led by Melvin Lyon, research professor of biological sciences in USC College. Lyon’s team sifted sonatas by Mozart and four other composers for the musical versions of “T-patterns”: highly unlikely, repeating combinations of specific notes separated by a constant time interval.

In addition to Mozart, the composers were Alexander Scriabin, known for his manic-depressive tendencies; Robert Schumann, almost certainly schizophrenic; and Johann Sebastian Bach and Franz Josef Haydn, both thought to be psychologically “normal.”

Previous studies have shown that schizophrenic patients exhibit more frequent and complex T-patterns in certain tests than control subjects.

Since schizophrenia and Tourette’s are related in their brain chemistry, Lyon predicted that Mozart also would show some T-pattern abnormality.

As expected, Schumann scored off the charts in Lyon’s study. Scriabin was next, followed by Mozart, who scored higher than Haydn and Bach.

“Although there was little difference between Haydn, Bach and Mozart in number of different T-patterns, in length and level [of] complexity, Mozart lies closer to Scriabin and Schumann,” Lyon concluded.

While adding that more study was needed, Lyon called T-patterns a “very sensitive” tool that “does pluck out those differences that show these people had a mental disturbance of some kind.”

Lyon speculated that schizophrenics struggle to make sense of everything they perceive, rather than granting priority to the task at hand or to the person in front of them.

“It’s not disorder, it’s really hyper-order,” Lyon hypothesized.

At the same time, Lyon added, a mild degree of mental disturbance can be a benefit to artistic production.

Lyon’s collaborators on the study were USC undergraduates Jingyi Li, Tyler Morgan and Evan Nunez. The group plans to write up the study for publication.