The neuroendocrine system links behavior and experience with hormone secretion. In turn, hormones act on the brain and other organs to regulate functions such as reproduction, fluid and mineral intake and balance, metabolism and activity of the immune system. They also help shape the developing brain, affect mood and behavior and contribute to aging and certain diseases.

Dr. McEwen studies the cellular and molecular mechanisms underlying the effects of stress and sex hormones on neurogenesis, synaptogenesis and dendritic remodeling in the hippocampal region of the adult brain. The hippocampus is a key structure involved in the formation of episodic, spatial and contextual memories, and it is one of the first brain structures to show degeneration in Alzheimer’s disease. His laboratory has found that hormone actions on structural plasticity intertwine with the actions of excitatory amino acid transmitters, serotonin, GABA and other neurotransmitters.

The McEwen lab is also studying neurogenesis in adult life, which occurs in the dentate gyrus of mammals from rodents to humans. It is regulated positively by exercise, an enriched environment and certain forms of learning; it is negatively regulated by certain types of stress and fear learning. Dr. McEwen’s lab is working to elucidate the neurochemical and hormonal factors responsible for the positive and negative regulation of neurogenesis, investigating factors such as neurotransmitters like serotonin and sex hormones (positive) and excitatory acids acting via NMDA receptors, opioids and glucocorticoids (negative).

His lab is also investigating the effects of chronic stress in both the dentate gyrus and the hippocampus. In the dentate gyrus, it appears to reduce neuron number and contribute to cognitive impairment. In the hippocampus, it causes neurons to undergo remodeling of dendrites. Excitatory amino acids — in particular NMDA receptors — are important regulators of neuronal remodeling, acting in concert with glucocorticoids and serotonin. The release and reuptake of the excitatory amino acid glutamate is a key process in modulating both remodeling of dendrites and dentate gyrus neurogenesis.

Estrogens cause neurons of the hippocampus to form new excitatory synaptic connections on dendritic spines of CA1pyramidal neurons, something that also involves the participation of NMDA receptors. Dr. McEwen has developed and is now testing a transsynaptic model for synaptogenesis that recognizes at least five sites of estrogen regulation.

His lab has recently expanded its scope of study to investigate stress-induced structural remodeling in two regions of the brain: the amygdala, which is involved in fear and strong emotions, and the prefrontal cortex, which is involved in working memory, decision making and extinction of fear learning, among other functions. In these brain regions, as well as the hippocampus, his laboratory is beginning to study how sex and stress interact — that is, how males and females differ in how they respond to stress.

Dr. McEwen’s research has helped create a new understanding of how the brain changes in structure and function in adult life as well as during development, and his findings have implications for understanding the impact of stress on the brain and sex differences in human brain function, abnormalities such as Alzheimer’s disease, depressive illness, post-traumatic stress disorder and the aging process.

CAREER

Dr. McEwen received his bachelor’s degree in chemistry from Oberlin College in 1959, and his Ph.D. in cell biology from Rockefeller in 1964. He was a U.S. Public Health Service Postdoctoral Fellow at the Institute of Neurobiology in Goteborg, Sweden from 1964 to 1965, worked as an assistant professor in the zoology department at the University of Minnesota, then returned to Rockefeller in 1966 as assistant professor. He was appointed associate professor in 1971, professor and head of lab in 1981 and was named Alfred E. Mirsky Professor in 1999.

Dr. McEwen is a past president of the Society for Neuroscience. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences and the Institute of Medicine. In 2006, he received the Pasarow Award in Psychiatry. He is a recipient of the Dale Medal of the British Endocrine Society, and in 2005 he received the Goldman-Rakic Prize for Cognitive Neuroscience from the National Alliance for Research for Schizophrenia and Depression and the Karl Lashley Award from the American Philosophical Society.