Researchers Receive NIMH Brain Awards

Two Boston University School of Medicine (BUSM) faculty members, Pietro Cottone, PhD, an assistant professor of pharmacology and psychiatry and Michael Silverstein, MD, an associate professor of pediatrics, were each awarded the prestigious National Institute of Mental Health (NIMH) Biobehavioral Research Awards for Innovative New Scientisits (BRAINS) grant with ten other investigators from around the country. The BRAINS award called for innovative and groundbreaking research projects from early stage investigators to explore the complex mechanisms underlying mental disorders or novel treatments and prevention strategies.

The BRAINS initiative was created to support the research programs and career development of outstanding scientists who are in the early, formative stages of their careers and who plan to make a long term commitment to research most relevant to NIMH. This award seeks to assist these individuals in launching an innovative clinical, translational, or basic research program that holds the potential to profoundly transform the understanding, diagnosis, treatment, or prevention of mental disorders.

Cottone, whose research explores the neural mechanisms underlying addictive disorders summarizes his proposal. "We propose that a history of dieting and relapse represents a vicious circle between stress and compulsive eating. In other words, the next attempt to avoid junk food is going to be more painful and stressful than the previous one, and the likelihood of relapse will progressively increase. We propose that during dieting the endocannabinoids (chemicals of the brains that protect from stress and promote the consumption of our favorite foods) are released to try to fight this stressful condition but on the other side they also increase our craving for junk food. Therefore blockade of the endocannabinoid action on one hand reduces compulsive eating, but on the other hand it induces anxiety and depression. This proposal will clarify the mechanisms linking eating disorders and obesity to anxiety and mood disorders."

Silverstein is studying maternal depression and is exploring detection and treatment options in the community setting, using for example, programs like Head Start and Early Intervention. He is experimenting with motivational interviewing and cognitive behavior therapy. "Our project is a community-based maternal depression prevention trial that enrolls young mothers at risk for developing major depressive disorder. The project takes place in Head Start and aims to enroll 230 women over five years."

"While these awards fund specific projects, they are truly an investment in specific people," said NIMH director Thomas R. Insel, MD. Inspired by the success of the NIH Director's Pioneer Awards and New Innovator Awards, both of which are designed to provide support for innovative research that has the potential for unusually high impact on health science. "The hope is that BRAINS awards will give early stage investigators enough flexibility to take risks on tough problems that are central to neuroscience and to the understanding of mental illness, such as the nature and development of neural circuits and the genetic factors and environmental influences that both shape and disrupt them," he adds.

The BRAINS program awards up to $1.625 million over five years for early career scientists focusing on a gap area identified in the Institute's Strategic Plan.

Source:
Gina DiGravio
Boston University Medical Center

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Researchers Identify Site In Brain Where Leptin May Trigger Puberty

UT Southwestern Medical Center researchers have pinpointed a tiny site in the brain where the hormone leptin may help trigger the onset of puberty.

The findings in mice indicate that a site within the hypothalamus called the ventral premammillary nucleus, or PMV, is the target where the hormone leptin effectively kick starts puberty in females.

Researchers have known that puberty starts when individuals have enough energy stores or fat to meet the demands of reproduction, and that leptin - a hormone produced by fat cells - acts in the brain to mediate this process, but the precise locale in the brain where leptin exerts this effect remained unclear.

"We found that the PMV is a key site of leptin action on puberty. This may not be the only site, considering the importance of the reproductive function for species survival, but the role played by PMV neurons has not been recognized before," said Dr. Carol Elias, assistant professor of internal medicine at UT Southwestern and senior author of the article available online and in the Jan. 4, 2011, print issue of the Journal of Clinical Investigation. "Our findings show that leptin action only in the PMV is sufficient to induce puberty in female mice."

Prior research has shown that in mice and humans lacking leptin, puberty grinds to a screeching halt at the prepubescent level, and the animals are infertile. Studies also have shown that reintroducing leptin to leptin-deficient people causes puberty to resume. Partly because of this, some researchers speculate that obese children may begin puberty earlier due to the higher levels of leptin produced by their fat tissues.

"We are witnessing an alarming situation in which the increasing incidence of childhood obesity may be inducing an advance in the onset of puberty in girls," Dr. Elias said. "The main obstacle for researchers in the field has been identifying the cell population involved in this event."

In this study, the researchers wanted to determine where leptin plays its role. To do this, they developed transgenic mouse models in which the mice had functional leptin receptors only in the PMV. Because of the lack of leptin signaling everywhere else in the body, the mice were obese but showed pubertal development and were able to get pregnant.

"One result that surprised us was that leptin acting only in the PMV was sufficient to induce puberty and improve fertility in females, but not in males," Dr. Elias said. "We're now trying to understand what's going on with males and whether leptin acts in different brain sites to induce puberty and fertility in males."

The next step, Dr. Elias said, will be to determine the molecular mechanism behind leptin's effects on puberty and reproductive control.

Notes:

Other UT Southwestern researchers involved in the study included Drs. Jose Donato Jr. and Roberta Cravo, co-lead authors and postdoctoral researchers in internal medicine; Dr. Renata Frazão, postdoctoral researcher in internal medicine; Dr. Lisandra Margatho, former postdoctoral researcher in internal medicine; Drs. Laurent Gautron, Michael Scott and Syann Lee, instructors of internal medicine; Charlotte Lee, senior research scientist; Dr. James Richardson, professor of pathology, molecular biology and plastic surgery; Dr. Roberto Coppari, assistant professor of internal medicine; Dr. Jeffrey Zigman, assistant professor of internal medicine and psychiatry; and Dr. Joel Elmquist, professor of internal medicine, psychiatry and pharmacology.

Researchers from the University of São Paulo, Acceleron Pharma, Rockefeller University and the Albert Einstein College of Medicine also participated.

The study was supported by the National Institutes of Health, the Foundation for Research Support of the State of São Paulo, and the Brazilian Federal Agency for the Support and Evaluation of Graduate Education.

Source:
Kristen Holland Shear
UT Southwestern Medical Center

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