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Peripheral vision

Medicine@Yale, 2011 - July August


To fully fathom the brain we can’t forget the body, says neuroendocrinologist

When it came time to choose a career as a young man in his native Hungary, family history was a strong influence for Tamas L. Horvath, D.V.M., Ph.D. His father’s side of the family is lined with veterinarians, his mother’s with physicians. His older brother was already planning to be a doctor, so although Horvath was both allergic to and afraid of animals, he thought his destiny must lie in veterinary medicine.

But Horvath had a deep interest in basic biomedical research, and after receiving a degree from the University of Veterinary Sciences in Budapest he changed course, coming to the School of Medicine as a postdoctoral fellow in 1990. “The flexibility of the American system was what brought me here,” Horvath says. “I didn’t really want to be a vet, so I immediately came to Yale.”

At the medical school Horvath worked with fellow Hungarian Csaba Leranth, M.D., now professor of obstetrics, gynecology, and reproductive sciences, and with Frederick Naftolin, M.D., Ph.D. (now at New York University School of Medicine), both leading researchers in the neural and hormonal bases of reproductive physiology and behavior. He joined the Yale faculty in 1996, and, in 2000, was awarded a Ph.D. in neurobiology from Attila József University in Hungary.

Horvath is now in his seventh year as chair of the medical school’s Section of Comparative Medicine, a discipline that dates back to the 1960s, when veterinarians in academic medicine and the pharmaceutical industry began applying insights from their research to the human condition. The field was a natural fit for Horvath, who also holds an appointment in the Department of Neurobiology, and who earlier this year was named the inaugural Jean and David W. Wallace Professor of Biomedical Research.

In the mid-1990s Horvath realized that the brain circuitry governing reproduction also plays a major role in hunger, eating, and obesity. He shifted his research focus, showing that ghrelin, a hunger hormone released when the stomach is empty, acts on the hypothalamus, a relatively primitive brain region that regulates feeding and a variety of other basic functions.

But Horvath wondered whether ghrelin could also affect higher brain functions. In 2006, he and his research team reported in Nature Neurosciencethat mice with higher blood levels of ghrelin performed significantly better on learning and memory tasks, and that the hormone stimulated the formation of significantly more synapses in the hippocampus, a brain structure crucial to memory. These findings could lead to ghrelin-based therapies for neurodegenerative illnesses like Alzheimer’s disease.

Findings like these have given Horvath a new and paradoxical perspective on neurobiology: by studying how the mammalian brain interacts with basic bodily systems, like the digestive system, to regulate metabolism, he believes we can better understand why humans have evolved with such a complex central nervous system.

“The mechanisms that set the brain’s ability to function are really driven by the peripheral tissues,” explains Horvath. “I’m not saying what makes us human is our liver or muscles, but these periphery systems are part of what shapes us to make decisions at the right time to keep us alive.”

Yale has become a new tradition for the Horvath family. Horvath’s wife and scientific collaborator, Sabrina Diano, Ph.D., is professor of obstetrics, gynecology, and reproductive sciences at the School of Medicine. And that older brother who wanted to become a doctor? That’s Balazs Horvath, M.D., assistant professor of anesthesiology.