Heads of Laboratories
Alfred E. Mirsky Professor
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology
Throughout life, hormones alter behavior and mood, regulate neuroendocrine activity, protect the brain from stress, and regulate brain aging and certain disease processes. McEwen’s laboratory takes an interdisciplinary approach to investigate how stress and sex hormones act on the brain. His work has wide-ranging implications for understanding how the brain changes from embryonic development through adult life.
The neuroendocrine system links behavior and experience with hormone secretion. Hormones, in turn, regulate body functions such as reproduction, fluid and mineral balance, metabolism, and immune activity. They also help shape the developing brain, affect mood and behavior, and contribute to aging and disease.
In studying the cellular and molecular mechanisms underlying the effects of stress and sex hormones on the hippocampus and other regions of the adult or developing brain, the McEwen laboratory has helped create a new understanding of how the brain changes in adult life and in development. Their work has implications for understanding the impact of stress on the brain and sex differences in human brain function as well as in Alzheimer’s disease, depression, posttraumatic stress disorder, and normal aging.
In relation to stress, the McEwen lab has shown that hormone actions on structural plasticity are intertwined with the actions of excitatory amino acid transmitters, NMDA receptors, other neurotransmitters, and BDNF. McEwen has also found that chronic stress reduces the number of neurons in the dentate gyrus. In the hippocampus, the lab has shown that chronic stress causes neurons to undergo remodeling of dendrites, and excitatory amino acids are important regulators of this neuronal remodeling, acting in concert with glucocorticoids. Stress-induced remodeling is largely reversed once the stress is removed, although gene expression patterns continually change with experience and resilience declines with aging.
The hippocampus is involved in the formation of episodic, spatial, and contextual memories, and is one of the first brain structures to degenerate in Alzheimer’s disease. The McEwen lab has recently shown that age-related impairment of cognitive function can be reduced by treatment with riluzole, a drug that reduces glutamate overflow.
In studying the action of sex hormones, the researchers have identified sex hormone receptors in the hippocampus that regulate signaling pathways associated with synapse formation and maturation. These “nongenomic” forms of the classical sex hormone receptors work in concert with the more classical genomic actions of sex hormones on gene expression, and they increase excitatory synapse formation and exert neuroprotective effects in the hippocampus and other brain regions.
The McEwen lab has recently expanded its scope of study to investigate stress-induced structural remodeling in the amygdala, which is involved in fear and strong emotions, and the prefrontal cortex, which is involved in working memory, self-regulation, and extinction of fear learning. In animals, aging leads to loss of the ability to promptly extend dendrites of the prefrontal cortex after cessation of stress.
Work conducted as part of the Neuroimmune-Physiology Program, headed by Karen Bulloch, has led to the discovery of dendritic-like cells in the brain that are activated by interferon-γ to present antigens. These cells increase in number in the aging brain, and are induced by viral infections and simulated stroke.
A.B. in chemistry, 1959
The Rockefeller University
Institute of Neurobiology, Gothenburg, 1964–1965
Assistant Professor, 1966
University of Minnesota
Assistant Professor, 1966–1971
Associate Professor, 1971–1973
Associate Professor with Tenure, 1973–1981
Associate Dean for Graduate and Postgraduate Studies, 1985–1991
Dean, Graduate and Postgraduate Studies, 1991–1993
The Rockefeller University
Dale Medal, British Endocrine Society, 2001
Karl Spencer Lashley Award, American Philosophical Society, 2005
Goldman-Rakic Prize, 2005
Gold Medal, Society of Biological Psychiatry, 2009
Fondation IPSEN Neuroplasticity Prize, 2010
Scolnick Prize in Neuroscience, Massachusetts Institute of Technology, 2011
The Gregory Pincus Medal, Worcester Foundation for Biomedical Research, 2013
Thomas W. Salmon Award, New York Academy of Medicine, 2015
Fondation IPSEN Endocrine Regulations Prize, 2017
National Academy of Sciences
National Academy of Medicine
American Academy of Arts and Sciences
Fellow, American Association for the Advancement of Science
Pereira, A.C. et al. Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole. Mol. Psychiatry 22, 296–305 (2017).
Bigio, B. et al. Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: implications for treatment resistance. Proc. Natl. Acad. Sci. U.S.A. 113, 7906–7911 (2016).
Gray, J.D. et al. Translational profiling of stress-induced neuroplasticity in the CA3 pyramidal neurons of BDNF Val66Met mice. Molecular Psychiatry online: December 13, 2016.
Gagnidze, K. et al. Nuclear receptor REV-ERBα mediates circadian sensitivity to mortality in murine vesicular stomatitis virus-induced encephalitis. Proc. Natl. Acad. Sci. U.S.A. 113, 5730–5735 (2016).
McEwen, B.S. et al. 60 years of neuroendocrinology: redefining neuroendocrinology: stress, sex and cognitive and emotional regulation. J. Endocrinol. 226, T67–T83 (2015).