Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology

Bruce McEwen

Bruce McEwen
Alfred E. Mirsky Professor

The adult brain is much more resilient and adaptable than previously believed, and adaptive structural plasticity involves growth and shrinkage of dendritic trees, turnover of synapses and limited amounts of neurogenesis in the forebrain, especially the dentate gyrus of the hippocampal formation. Our laboratory investigates how the brain undergoes changes in response to experiences, acting, in part, via the internal environment of the body in the form of circulating hormones. Hormones of the gonads and adrenal glands regulate neuronal structure (synapse formation, remodeling of dendrites, and neurogenesis) as well as neurochemistry in the adult brain via genomic and non-genomic receptors that work in concert with neurotransmitters, such as glutamate, as well as other mediators, such as brain derived neurotrophic factor (BDNF), tissue plasminogen activator and endocannabinoids. Estrogens and androgens induce new synaptic connections in brain areas such as the hippocampus, a structure that is important in learning and memory. These same hormones also modulate damage produced in stroke, head trauma and seizures (glucocorticoids exacerbating damage; estrogens and androgens protecting against damage). Age-related changes in brain function and cognition are also likely to involve decreasing influences of gonadal hormones and increasing effects of adrenal glucocorticoids and other mediators such as inflammatory cytokines.

We investigate stress effects upon brain centers involved in emotion and fear memory, such as amygdala, and brain regions involved in contextual and episodic learning and memory as well as mood control, such as the hippocampus and prefrontal cortex. These brain regions all turn out to be sensitive to the effects of sex and stress hormones via both genomic and non-genomic receptors. Besides stressors that generate anxiety and learned helplessness, we also investigate the neural and behavioral consequences of circadian disruption such as arises from shift work, jet lag and sleep deprivation.

In studying both stress and sex hormones as regulators of structural plasticity in the adult brain, it is necessary to consider sex differences and how they develop. Adverse early life experiences also have long-lasting effects on brain development, learning and memory, as well as predisposition towards disease. Although our laboratory does not do translational studies on human clinical populations, we collaborate with investigators who do such studies. Moreover, through national organizations that are concerned with human well being, we apply this knowledge to early childhood development and the effects of socioeconomic status on brain and body health.