60 YEARS OF NEUROENDOCRINOLOGY: Redefining neuroendocrinology: stress, sex and cognitive and emotional regulation

    1. Carla Nasca
    1. Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    1. Correspondence should be addressed to B S McEwen; Email: mcewen{at}rockefeller.edu


    The discovery of steroid hormone receptors in brain regions that mediate every aspect of brain function has broadened the definition of ‘neuroendocrinology’ to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive. But, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic anxiety and depression. There are important sex differences in the brain responses to stressors that are in urgent need of further exploration. Moreover, adverse early-life experience, interacting with alleles of certain genes, produce lasting effects on brain and body over the life-course via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain–body interactions.

    • Received in final form 17 March 2015
    • Accepted 1 May 2015
    • Made available online as an Accepted Preprint 1 May 2015
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