A University of Toledo faculty member provided a glimpse into the aging mind during a worldwide conference in July.

Pasupuleti

Dr. Sudershan Pasupuleti, associate professor of social work and Hartford Geriatric Faculty Scholar, has conducted potentially groundbreaking research on the “rebound” capacity of the aging brain. He presented preliminary results of his studies at the 19th International Association of Gerontology and Geriatrics World Congress of Gerontology and Geriatrics in Paris. The conference, which takes place every four years, was attended by more than 3,000 people from disciplinary backgrounds. His audience was comprised of physicians, psychologists, social workers, researchers and others who work in this specialized field.

Pasupuleti’s topic was “Cognitive Enhancement Among Older Adults: An Integrated Approach,” which provided a glance into studies he’s conducted as one of 10 inductees in the Hartford Faculty Scholars Program in 2008.

In partnership with PositScience Corp., Pasupuleti is examining whether a series of computerized stimulation exercises can improve cognitive functioning. San Francisco-based PositScience provided the specialized software; more than a dozen senior centers and senior housing facilities have partnered with Pasupuleti to participate in the brain fitness program over eight to 10 weeks.

“Cognitive ability is the key to independent living and quality of life,” Pasupuleti said. “Cognitive decline in the older adult population leads not only to emotional distress, but to financial challenges, as well.”

Noting that cognitive impairment is one of the primary reasons older adults seek supplemental living arrangements, he said even slight improvements can decrease reliance on family support, health-care resources and mental health services.

“An integrated approach is needed to improve cognitive function among older adults to not only delay age-related decline, but also to prevent impairment and dementia with engaged lifestyle through physical, mental and social activities,” Pasupuleti said.

“Much of my research is in progress,” he added. “I have learned a lot in the field and finding some cutting-edge areas for my future research is gratifying for me.”

Pasupuleti plans to host a workshop open to professionals in clinical and academic fields after evaluation of his research in the spring.

He will study additional intervention methods with the goal of presenting treatment choices to those within the aging population. His $100,000 award as a Hartford Faculty Scholar allows his research to continue through next year.

As the northwest Ohio economy transitions toward one driven by alternative energy, a new $5 million grant from the National Science Foundation will help The University of Toledo, Toledo Public Schools and several supporting partners prepare today’s K-12 students for jobs in the new work force.

The goal of the Leadership for Educators: Academy for Driving Economic Revitalization in Science (LEADERS) partnership is to improve K-12 science education and make it more interesting to students by incorporating hands-on or Project-Based Science linked to the renewable energies industry and its environmental impacts, which are vital to the economic development of the Great Lakes region.

“Project-Based Science contextualizes learning so that it is interesting to students,” said Dr. Charlene Czerniak, UT professor of curriculum and instruction and a co-investigator on the grant. “Often the curriculum is based around a driving question, such as ‘Is water in Lake Erie safe to drink?’ Then lessons about invertebrates, sustainable energy and climate change are tied back to answering that question.”

Over the duration of the LEADERS project, 24 teachers from four school districts — two each from elementary, middle and high school levels — will take two-and-a-half summers of graduate courses in physics, chemistry, environmental science and engineering. UT scientists and science educators will partner to teach the courses and blend the content with Project-Based Science activities that the K-12 teachers will then implement in their classrooms.

The project will launch in summer 2010 with Toledo Public Schools and Toledo Diocese Schools. Akron City Schools and Monroe County Intermediate School District teachers will begin training in summer 2012.

“It is critical that our students learn the skills that will be expected of them in the work force,” said Jan Kilbride, chief academic officer of Toledo Public Schools and a co-investigator on the project. “This project will allow teachers to improve their content expertise and better relate their lessons to events to which the students have a connection.”

During the first summer, the K-12 teachers will take courses in Physical Principles of Energy Sources for Humans, Principles of Solar and Wind Energy, Problem-Based Science and Leadership.

Upon returning to their districts, the teachers will assume the roles of teacher leaders and work with their colleagues so that the whole district is impacted.

“We have a history of teacher leaders playing a role in curriculum development, and this is another great step,” Kilbride said.

Dr. Kevin Czajkowski, UT associate professor of geography and a co-investigator, said the LEADERS project can revolutionize the way the community views and provides education.

“In addition to enticing students to pursue careers in alternative energy, I hope we can improve the general population’s science knowledge and the acceptance of renewable energy,” Czajkowski said.

The LEADERS project links national science standards with the expected skill sets of science practitioners, resulting in K-12 lessons that are not only challenging, but also relevant.

“Linking Project-Based Science to economic development challenges the paradigm that teachers simply follow state and national standards,” Czerniak said. “If a curriculum leads to kids getting a job in the community, that is economic development. We want K-12 teachers to begin thinking of the role they play in our changing economy.”

By its conclusion, an estimated 86,000 K-12 students are expected to benefit from the LEADERS program.

Supporting partners in the LEADERS project are Akron area schools, Toledo Diocese Schools, Monroe County Intermediate School District, Monroe County Community College, Toledo Science Center, TechniGraphics, Blue Water Satellite, the Wright Center for Photovoltaics Innovation and Commercialization, and the Great Lakes WIND Network.

The University of Toledo set an institutional record in fiscal year 2009 for sponsored-research funding, bringing in more than $70 million for the first time in its history.

The $70.8 million total is 12 percent more than the previous record high of $63 million in 2007.

In all, UT received 517 awards, including three Ohio Third Frontier grants totaling almost $14 million.

Dr. James Trempe, senior director of research administration, said the overall increased funding is directly correlated to an increase in grant proposals submitted by faculty members.

“During tough times, people have to step up to the plate, and our faculty here at UT are working very hard,” Trempe said.

In addition to those submitting grants, the University’s Office of Innovation Enterprises has been busy. UT Innovation Enterprises is a new office that brings together research development, technology transfer, incubation, work-force development, campus-wide research institutes, and the previous Science and Technology Corridor operations.

“I am pleased with the hard and tireless work of Dr. Elsa Nadler [director of grants development] in assisting the coordination and submission of large, multi-investigator and multidisciplinary proposals,” said Dr. Frank Calzonetti, vice president for research and economic development.

Calzonetti and Trempe encourage faculty members to contact the offices of Innovation Enterprises and Research and Sponsored Programs with questions about submitting competitive proposals. The Office of Innovation Enterprises also has available funds for cost-sharing to better position UT to compete against other major research universities.

Not only is research funding a major factor in how universities are ranked, it also can have a ripple effect around campus. Research funding typically helps retain talented researchers and recruit new scientists who already have large grants they can bring to Toledo. Those scientists then can help enhance UT’s academic rigor and student experience.

“Perhaps the most important element of our success is the increased number of faculty members on campus who have excellent research credentials, great ideas, and the drive to support their research through external funding,” Calzonetti said. “Our increased grant and contract activity enhances our stature as a growing research university.”

In addition to hard work being done at UT, Calzonetti acknowledged the support of U.S. Congresswoman Marcy Kaptur and Sen. George Voinovich and Sen. Sherrod Brown in assisting UT with funding and access to funding opportunities.

To many medical professionals, embryonic stem cells hold the future key to regenerative medicine and tissue replacement after injury and diseases such as diabetes, Parkinson’s disease, traumatic spinal cord injury, muscular dystrophy, heart disease, and vision and hearing loss.

A team of UT College of Medicine researchers has studied embryonic stem cells and their capacity to self-renew and differentiate into more than 220 cell types, known as pluripotency, and the importance of fully utilizing this capacity.

A recent issue of the Journal of Cellular Physiology included the article titled “Chromatin Remodeling in Embryonic Stem Cells: The Balance Between Pluripotency and Differentiation,” and featured a figure from the article on the front cover.

The joint lead authors of the article are Dr. Ivana De La Serna, assistant professor of biochemistry and cancer biology, and Bridget Keenen, predoctoral student in the Biomedical Sciences Graduate Program.

“In order to maximally utilize the potential of embryonic stem cells for clinical application, it will be important to understand the processes that maintain pluripotency as this ability is lost when cells become differentiated to a particular cell type,” De La Serna said.

The article focuses on epigenetic, or external mechanisms, that regulate embryonic stem cell pluripotency.

“Epigenetics involves the stable regulation of gene expression by mechanisms that do not result in changes in DNA sequence,” De La Serna explained. “One important epigenetic mechanism for controlling gene expression involves change in chromatin structure.”

De La Serna’s figure chosen for the journal cover is a bivalent mark on the chromatin that is distinctively a characteristic of embryonic stem cells. These marks are thought to be an important determinant of embryonic stem cell pluripotency because they prime specific genes for activation when the appropriate cues are presented.

“We were very pleased to see our figure on the front cover of the journal because it emphasizes the importance of chromatin structure in the regulation of gene expression,” De La Serna said.

More and better data are needed to determine what types of approaches work best in combating childhood obesity, according to a University of Toledo pediatrician.

Dr. Joan Griffith talked about the dangers of overeating with patient Miesha Richardson.

Dr. Joan Griffith, associate professor and interim chief of general pediatrics, reviewed the practices of 80 childhood-obesity prevention programs administered by schools, academic teaching hospitals, community hospitals, clinics, health-care plans, community health centers and other groups across the country, hoping to identify what she called “a best practice for addressing childhood obesity in low socioeconomic and diverse communities.” She also analyzed recommendations of a 1998 national childhood obesity expert committee and interviewed five key childhood obesity authorities.

However, her study was not able to identify the best practice because of variations and inconsistencies in the programs’ data-collection efforts. For example, only 49 of the 80 programs she examined provided outcomes data.

Her study, “Assessing Childhood Obesity Programs in Low Socioeconomic and Diverse Communities,” was the result of work she did while earning a master of public health degree in 2007 from Harvard University, where she completed the Commonwealth Fund/Harvard University Fellowship in Minority Health Policy Program. It appeared in the May issue of the Journal of the National Medical Association.

“Our results imply that improvement in data collection/documentation by childhood obesity program leaders is the linchpin to identification of evidence-based effective interventions,” Griffith said.

Given the magnitude and the complexity of the problem, she said there is an urgent need to evaluate what are thought to be the best practices and evaluate their long-term effectiveness.

“If we are looking to determine the best practices, it’s critical that information is based on scientific evidence,” she said.

Griffith said the study provides some evidence that programs that encourage lifestyle changes, focus on the family, emphasize prevention and involve the community do the best job when it comes to gathering and analyzing data.

Generally recognized as a health time bomb, childhood obesity is linked to an increased risk of health problems later in life, including cancer, heart problems and diabetes. While genetics plays a role, Griffith said the culprits are increased consumption of unhealthy, calorie-laden fast foods and lack of physical exercise.

The obesity epidemic, she said, won’t be solved overnight because it is multifaceted. Parents, pediatricians, nurses, nutritionists, schools, hospitals, clinics, community health organizations, businesses and government all have roles in preventing and reducing childhood obesity.

Parents need to take the initiative by monitoring the amount and kinds of food their children eat, by providing nutritious meals, and by watching how much kids exercise, according to Griffith. They also should eat the way they want their children to eat and make sure their children are not watching too much television or spending too much time with video games, computers and cell phones. Parents who are concerned about a child’s weight should talk to their pediatricians and try to implement some simple steps to improve health.

“Parents should set the example by being active with their children,” she said. “We have become a technologically advanced country to our detriment. Too many children spend too much time sitting in front of the television.”

School systems can provide physical education and nutrition education and need to pay attention to what they are feeding children, she said. Cities must have parks and bicycling and walking lanes to encourage children to exercise.

“It is much better to prevent childhood obesity than to reverse it,” she said.

Griffith spent 21 years in the U.S. Air Force as a physician, retiring as a colonel, before moving into academic medicine.

A study by a University of Toledo radiologist has found that a 3T MRI is more accurate in detecting breast cancer than the more commonly used mammography and sonography.

Dr. Haitham Elsamaloty and UT Medical Center’s 3T MRI

Results of the findings were published in last month’s issue of the American Journal of Radiology.

Lead author of the paper, Dr. Haitham Elsamaloty, associate professor of radiology, said, “Our study suggests an important role for 3T MRI, especially for women who are at a high risk of breast cancer, in early diagnosis and in accurately evaluating the extent of disease, which is a crucial factor in planning appropriate therapy.”

The objective of the study was to assess the sensitivity and specificity of 3T MRI compared with those of mammography and sonography in the evaluation of breast cancer. In other words, how accurately could the 3T MRI detect disease or abnormality without missing any positive cases, while at the same time not suggesting any false positives? The study also sought to compare the 3T to previous MRI machines.

The study was conducted between May 2006 and October 2007 when 434 women at high risk of breast cancer underwent breast MRI, mammography and sonography in the Department of Radiology at The University of Toledo Medical Center. Patients were considered at high risk of breast cancer if they had a personal or strong family history of breast cancer or a positive genetic breast cancer test result.

The study results found the 3T MRI is more sensitive than mammography and sonography in the detection of breast cancer and in characterization of small lesions, but it also results in some false-positive results. Specifically, the 3T MRI correctly detected 100 percent of the study’s 66 true malignant lesions compared with 81.8 percent accuracy with mammography and 86.4 percent accuracy with sonography.

However, the 3T also suggested 49 masses to be malignant that ended up being confirmed benign by biopsy.

Elsamaloty said because use of MRI in detecting breast cancer is relatively new compared to the other methods, its specificity is expected to increase with experience.

Compared with previously published results, the study also found the 3T MRI has a higher sensitivity than the 1T and 1.5T versions in the detection of breast cancer with no significant difference in specificity.

All in all, Elsamaloty believes the study demonstrates that 3T MRI is an important tool in conjunction with mammography and sonography in the detection of breast cancer.

“We feel that our study will have a positive effect on the future and advancement of 3T breast MRI,” Elsamaloty said. “It will encourage us and other researchers to pursue further work in this area.”

Although the 3T MRI is clearly more effective than mammography and sonography, it is currently used primarily for high-risk patients because routine screening remains prohibitively expensive.

Seventeen UT students traveled to the University of Wisconsin-La Crosse last month to participate in the National Conference on Undergraduate Research (NCUR).

Kristin Stroud, a junior majoring in art and media studies, boarded the bus for the conference with one of her paintings that was inspired by African art.

The conference promotes undergraduate student achievement and creative activity in all fields of study. Of the usual 3,000 applicants each year, only 2,000 are accepted.

This is the second year that UT’s student researchers achieved a 100 percent acceptance rate to the conference.

“Whenever 2,000 top undergraduate students from all over the United States meet at the NCUR site, they always bring with them a lot of excitement and energy to the event. The students from UT are always ready for this challenging opportunity, and their presentations are always very polished and well-received,” said Dr. Larry Connin, UT administrative coordinator for the Honors Program.

“Going to events like NCUR gives our students a big advantage in applying for graduate or professional schools as they look to continue their education at the next level,” Connin added.

Students who attended the NCUR April 16-18 and the titles of their research were:

• Anthony Bradfield, a junior majoring in economics — “Premiums to College Five, 10 and 15 Years After Graduation.”

• Brittany Brinley, a senior majoring in biology — “SH2B1BETA Actin-Binding Sites Needed for Enhancement of Growth Hormone Cell Ruffling.”

• Tan Carlin, a senior majoring in health sciences and public health — “Availability of Language Services in Retail Pharmacies in the State of Ohio.”

• Abdulmajed Dakkak, a senior majoring in computer science — “Concurrency and Programming Languages.”

• Alison Fedyna, a senior majoring in biology — “TCR Alpha-Chain Usage in the NOD Model of Experimental Autoimmune Encephalomyelitis.”

• Noah Gillespie, a senior majoring in economics — “Measuring Socially Just Development: Transforming the Failures of the Past Into the Promise of the Present.”

• Danielle Hayden, a senior majoring in biology — “Determining the Role of the Tail Domain IFA-2 Function and Localization.”

• Nicole Kahle, a senior majoring in kinesiology and exercise science — “The Effects of Core Stability Training on Balance Testing in Young, Healthy Adults.”

• Steven Lombardo, a junior majoring in biology — “The Development of Monoclonal Antibodies Against the Tumor-Associated Protein Muci.”

• Brian Muntean, a junior majoring in chemistry — “The Design and Synthesis of Quinone-Capped Molecular Wires as Electrocatalysts for Detection of Thiols.”

• Jessica Pellman, a senior majoring in pharmaceutical sciences and toxicology — “Development of M5 Muscarinic Acetylcholine Receptor Antagonists.”

• Michele Phillips, a senior majoring in microbiology and immunology — “IL-13 Induced Regulation of Autoreactive T-Cells.”

• Sarah Siegel, a senior majoring in biology — “Role of C-Terminal Region of the G-CSF Receptor in Regulating ELA2 Expression in Myeloid Cells.”

• Stacy Snyder, a senior majoring in cell and molecular biology — “Deletion of SH2B1BETA Actin-Binding Sites Causes an Inhibition of Prolactin-Dependent Ruffling.”

• Amanda Stewart, a senior majoring in biology — “Interaction Between Mixed Lineage Kinase 3 and the Tumor Suppressor Protein Merlin.”

• Kristin Stroud, a junior majoring in art and media studies — “Acrylic on Canvas: A Series of Three Paintings Inspired by African Art.”

• Erin Swedish, a junior majoring in psychology — “Forensic Interviewer Fatigue: Does It Influence Interview Quality?”

Dr. Tom Barden, director of the UT Honors Program, who accompanied the students to the conference, said, “The University of Toledo was extremely well-represented this year. I know our reputation was enhanced by the quality of their presentations and the way these students answered questions at the poster sessions. I was very proud of them.”

The University of Toledo has been committed to becoming a national leader in the area of technology transfer. Each year, UT continues to increase activity in tech transfer, and 2009 is predicted to have the greatest success.

With the help of Samuel Giles, patent licensing associate in the Office of Research Development, right seated, Jack Harley of the JWH Group Inc., left, signed an exclusive license agreement for a gas sensor technology developed by Dr. Abdul-Majeed Azad from the UT College of Engineering. On hand for the signing were, from left, Stephen Snider, director of technology licensing and contracts, Dr. Dan Kory, associate vice president for technology transfer, and Mark Fox, patent-technology associate.

Even with two months until the end of the 2009 fiscal year, UT has already increased the number of invention disclosures, new license agreements and total license agreements from 2008.

For example, from 2008 to 2009, the number of invention disclosures grew from 55 to 72, new license agreements increased from 12 to 17, and total license agreements jumped from 85 to 99.

In addition, three spin-off businesses have been established with three additional businesses in the finalization process. This is a significant increase over the three established in 2008.

“We are very pleased with the increased level of involvement the Technology Transfer Office has received in the past couple of years,” said Stephen Snider, UT licensing and contracts director. “In the past five years, UT has spun out 13 new ventures and entered into 72 license agreements, which will improve the human condition.”

Two University of Toledo graduate students are recipients of coveted Ruth L. Kirschstein National Research Service awards for individual predoctoral research fellowship training from the National Institutes of Health.

Terry Hinds Jr., second from left, and Damien Earl, third from left, are recipients of NIH National Research Service awards for individual predoctoral research fellowship training. Also pictured are Hinds' adviser, Dr. Edwin Sanchez, and Dr. Elizabeth Tietz, who is Earl's adviser.

Damien E. Earl, an MD/PhD student in the College of Medicine, received a four-year award from the National Institute on Drug Abuse (NIDA), while a two-year award to Terry D. Hinds Jr., a PhD student in the College of Graduate Studies, is from the National Institute of Diabetes and Digestive and Kidney Diseases.

A Salem, Ohio, native and 2005 graduate of Kent State University, Earl is a student in the neurosciences and neurological disorders track and studies in the laboratory of Dr. Elizabeth I. Tietz, professor of physiology/pharmacology.

Earl’s award is for almost $161,000, which includes a stipend and monies for tuition, books and travel to scientific meetings. It runs through May 2013.

Currently in his second year of graduate studies, Earl has completed the first two years of medical school and will resume his medical studies after he finishes the requirements for the PhD.

Using rats as a model, he is studying molecular changes in the brain during withdrawal from benzodiazepines, a class of drugs — the best known of which are Valium and Xanax — most often prescribed for anxiety and insomnia. However, because it is relatively easy for people to become physically dependent, they have become drugs of abuse.

“We have found that elevated calcium levels inside certain neurons in the brain may be linked to withdrawal anxiety,” Earl said. “This may be due to aberrant regulation of a particular protein known as the voltage-gated calcium channel. My studies are focused on determining how this protein is regulated in rats chronically treated with Flurazepam. The goal is to find new therapeutic targets for treating benzodiazepine dependence, which will increase the clinical usefulness of this relatively safe class of drugs.”

After graduation, Earl plans to complete residency training and hopes eventually to obtain a position at an academic health center where he can practice medicine, conduct research and teach.

Tietz and Dr. David Giovannucci, associate professor of neurosciences, sponsored Earl’s fellowship application.

A native of Franklin Furnace in Scioto County and a 2002 graduate of Shawnee State University, Hinds is studying in the Center for Diabetes and Endocrine Research (CeDER) under the tutelage of Dr. Edwin Sanchez, professor of physiology/pharmacology and CeDER assistant director, who sponsored his application. The two-year award is for $75,000, which includes a stipend and monies for tuition, books and travel to scientific meetings.

Hinds’ studies focus on genetic factors involved in obesity.

“Factors that control obesity via dietary intake or therapy are of much interest,” he explained. “Unsaturated fatty acids, especially polyunsaturated fatty acids, have been shown in clinical and animal studies to be useful in controlling lipid storage and regulating body weight and obesity in mammals. The molecular mechanisms behind what controls these actions are not well understood. Diseases such as Cushing syndrome, obesity, type 2 diabetes and cardiovascular disease have been linked to the actions of cortisol on the body. Inside cells, cortisol binds to the glucocorticoid receptor, and this acts as a signal in regulating several different genes that regulate obesity and inflammation.

“Our laboratory has recently uncovered a promising approach that involves regulation of the receptor by TPR proteins, which can bind fatty acids and may regulate actions of cortisol on the body. We are investigating how different dietary fatty acids regulate obesity via TPR proteins that, in turn, regulate the glucocorticoid receptor. These studies should give insight into how our diet influences our gene expression and development of obesity.”

Hinds and Sanchez are submitting a provisional patent on their new discovery that will aid in understanding metabolism, obesity and diabetes. After graduation, Hinds plans to continue working with Sanchez on their discovery in hopes of developing a company. He eventually hopes to teach and conduct research at an academic health center.

Two MD/PhD graduates of the former Medical College of Ohio who worked in Tietz’s lab — Drs. Scott M. Lilly and Bradley Van Sickle — also were recipients of NIDA research service awards. Lilly, a 2006 graduate, is completing his third year of residency training in internal medicine at the University of Pennsylvania, while Van Sickle, a 2004 graduate, is a fellow in pediatric endocrinology at Vanderbilt University, where he is studying the interaction between faulty glucose regulation and the progression of cystic fibrosis.

Disco biscuits. Love doves. Shamrocks.

Colorful street nicknames, to be sure, but don’t be fooled by the recreational drug ecstasy and its close cousin, methamphetamine, said Dr. Bryan Yamamoto. They hold the potential of causing long-term damage to brain cells controlling mood, feelings of pleasure and emotions.

The laboratory research of Dr. Bryan Yamamoto is aimed at helping uncover the long-term health dangers of the party drugs ecstasy and methamphetamine.

Yamamoto, professor and chairman of the College of Medicine’s Department of Neurosciences, applies a wide-ranging research program to the dangers the two party drugs pose to the brain. He joined the UT faculty last year from the Boston University School of Medicine and has enjoyed continuous funding from the National Institutes of Health since 1986.

His studies, funded with grants totaling $1 million a year, could be used to develop better ways to prevent and treat drug abuse and to help develop therapies to fend off Parkinson’s and Huntington’s disease and other neurological disorders.

In low doses, methamphetamine and ecstasy generate feelings of euphoria and alertness — part of the brain’s so-called reward center — through the release of brain chemical messengers dopamine and serotonin. The drugs can increase blood pressure and heart rate and dangerously constrict blood vessels.

A growing concern, according to Yamamoto, is that the drugs may harm the brain over the long run. Methamphetamine causes the brain to produce free radicals — highly reactive molecules that kill brain cells, including those that produce dopamine and serotonin. Both drugs exhaust the brain’s supply of serotonin or dopamine, possibly by causing serotonin and dopamine transporters to reverse direction, pumping serotonin and dopamine out of neurons instead of sucking them back in. Some studies suggest that ecstasy — classified by the federal government as a drug with no known medical use and high potential for abuse — actually kills cells that produce serotonin.

The damage ecstasy causes to serotonin-producing cells, in fact, is oddly familiar, noted Yamamoto: “We are discovering that all these players involved in mediating the toxicity of amphetamines and ecstasy appear to be the same types of mechanisms that have been linked to the damage produced by Parkinson’s and Huntington’s disease. There are very close parallels to both of those drugs.”

“Free radicals have been implicated in mediating the damage in these diseases,” he continued. “By understanding how those free radicals are being produced, maybe we can understand the underlying causes of these diseases. These drugs are providing a valuable tool to produce and then better understand the damage.”

A major focus of his rat studies is the relationship between chronic stress and brain mechanisms affecting drug-use behaviors. In 2003, he was the first to demonstrate that if the animals are exposed to chronic stress prior to being given amphetamines, the drugs’ neurotoxicity dramatically increases. The findings appeared in the journal Psychopharmacology.

In vivo microdialysis studies allow him to peer inside the rats’ brains with probes that simultaneously monitor and record the release of dopamine at timed intervals and record the neural activity. “Most drug abusers are under a lot of stress — psychological stress, environmental stress,” he explained. “Many sufferers of post-traumatic stress syndrome have substance-abuse disorders. We are interested in examining how stress impacts the neurotoxicity of these drugs.”

An FDA-approved clinical trial is under way in South Carolina to determine whether ecstasy will benefit people, such as returning U.S combat troops, suffering from post-traumatic stress disorder. “Our animal studies would suggest that this is a very bad combination because chronically stressed individuals are more vulnerable to the toxic effects of these drugs,” Yamamoto said.

He also is studying how ecstasy can compromise neurons in the brain by damaging their mitochondria — the structures responsible for cellular energy production — causing the cells to essentially lose power.

Yamamoto’s research teams have made several significant findings. In 1992, he was the first researcher to demonstrate that at excessive levels, the brain amino acid glutamate is toxic, causing nerve cell stress that ends in cell death. The finding appeared in the journal Brain Research.

In 2005, he discovered in animal studies that by damaging the blood-brain barrier, a physical and chemical entity that provides a protective, stable environment for the brain, ecstasy leaves the brain vulnerable to invasion by viruses and other pathogens. His rat studies showed this vulnerability even 10 weeks after the initial exposure to the drug.