“We congratulate Bruce McEwen on being selected for this award” said Robert Desimone, director of the McGovern Institute and chair of the selection committee. “For over four decades, he has been a pioneer in understanding how hormones affect the brain; how they affect its structure, how they shape responses to stress, how they contribute to sexual differences, and how they affect our health and well-being.”
McEwen’s first major discovery was the existence of corticosteroid receptors in the brain. Corticosteroids are a class of hormones released by the adrenal gland that control, among other things, the body’s response to stressful experiences. In a classic 1968 paper, McEwen demonstrated the existence of corticosteroid receptors in the rat hippocampus, a brain region important for memory and learning. In a series of subsequent studies, he examined the role of these hormones and their receptors in regulating the brain’s response to stress, including effects on gene expression, cell structure and behavior.
Stress produces many changes in the brains of animals and humans, including brain atrophy and memory impairment. McEwen and colleagues showed that these phenomena occur in many brain regions, and provided a cellular explanation for the changes, showing that when corticosteroids bind to their receptors in hippocampus, they trigger a retraction of dendrites, the finely branched structures that receive signals from other neurons. In 1986, with his then-student Robert Sapolsky and postdoctoral associate, Lewis Krey, he put forward the "glucocorticoid cascade" hypothesis, now widely accepted as an explanation for the effect of chronic stress. According to this hypothesis, when glucocorticoid hormones are released in response to stress, they cause damage to the brain circuits that regulate their own release, thereby creating a vicious circle of further release and damage to the brain.
McEwen’s second major contribution has been to show how sex hormones affect the brain. He and his then-student Richard Zigmond were the first to biophysically characterize brain receptors for the sex hormone estradiol, the major form of estrogen in humans. Estradiol is made primarily in the ovaries, but McEwen showed that it is also made in the brain, through the action of an enzyme called aromatase that converts testosterone to estradiol. He studied how estrogens affect neuronal gene expression and the fine structure of brain cells, including the formation and maintenance of synapses in the hippocampus. These effects and similar effects in other brain regions, are thought to underlie the influence of estrogens on cognitive function as well as differences in mood and anxiety-related behavior and stress-reactivity between the sexes, and may also underlie many of the effects of estrogen replacement therapy in post-menopausal women. McEwen continues to study basic mechanisms of sex hormone action, including the molecular signaling pathways by which estrogens affect synaptic function.
With more than 900 papers to his name, McEwen’s work spans many other fields of neuroscience in addition to neuroendocrinology. For example in one early breakthrough, he and his colleague Bernice Graftstein were the first to demonstrate fast axonal transport, a fundamental mechanism by which axons carry proteins and other materials to their growing tips, supporting their outgrowth and remodeling over time. McEwen’s influence extends beyond his own work; many of the leading researchers in the field of neuroendocrinology trained in his lab, and he has also been an exceptional public advocate for brain health; he is a regular advisor to the National Scientific Council on the Developing Child and the National Academy of Sciences and Institute of Medicine, and, as president of the Society for Neuroscience, he launched the popular "Brain Awareness Week" program. Most recently, he has been studying the relationship between socioeconomic status, stress and health, and he has coined the term ‘allostatic load’ to describe the cumulative detrimental effects of chronic stress on body and brain. He has argued that life adversity exacerbates this load, and that many disparities in health outcomes can be traced to the biological effects of stress that begin in early childhood and even in utero.
The McGovern Institute will award the Scolnick Prize to Dr McEwen on Sept. 26. At 4 p.m. he will deliver a lecture titled "Sex, Stress and the Brain: hormone actions above the hypothalamus via novel mechanisms," to be followed by a reception at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar St. (MIT 46-3002) in Cambridge. The event is free and open to the public.
About the Edward M. Scolnick Prize in Neuroscience
The Scolnick Prize, awarded annually by the McGovern Institute, is named in honor of Dr. Edward M. Scolnick, who stepped down as President of Merck Research Laboratories in December 2002 after holding Merck's top research post for 17 years. Dr. Scolnick is now at the Broad Institute, where he directs the Stanley Center for Psychiatric Research. He also serves as a member of the McGovern Institute’s governing board. The prize, which is endowed through a gift from Merck to the McGovern Institute, consists of a $60,000 award, plus an inscribed gift. Previous winners are Lily and Yuh-Nung Jan (University of California, San Francisco), Jeremy Nathans (Johns Hopkins University), Michael Davis (Emory University), David Julius (University of California, San Francisco), Michael Greenberg (Harvard Medical School), Judith Rapoport (National Institute of Mental Health) and Mark Konishi (California Institute of Technology).