McEwen Bruce S, Gray Jason D, Nasca Carla
Laboratory of NeuroendocrinologyThe Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
Laboratory of NeuroendocrinologyThe Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
J Endocrinol. 2015 Aug;226(2):T67-83. doi: 10.1530/JOE-15-0121. Epub 2015 May 1.
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.
在介导脑功能各个方面的脑区中发现类固醇激素受体，拓宽了“神经内分泌学”的定义，使其包括大脑与身体之间通过激素和神经通路进行的相互交流。大脑是应激和对应激适应的中枢器官，因为它能感知并确定什么是威胁，以及对应激源的行为和生理反应。成年大脑和发育中的大脑在应激反应方面具有显著的结构和功能可塑性，包括神经元替代、树突重塑和突触更新。应激会导致维持认知、决策、焦虑和情绪的神经回路失衡，从而改变这些行为和行为状态的表达。反过来，这种失衡会通过神经内分泌、自主神经、免疫和代谢介质影响全身生理。在短期内，比如在威胁环境中增加恐惧警惕性和焦虑，这些变化可能具有适应性。但是，如果危险过去而行为状态以及神经回路的变化持续存在，这种适应不良可能需要药物治疗和行为治疗相结合的干预，慢性焦虑和抑郁症就是这种情况。大脑对应激源的反应存在重要的性别差异，亟待进一步探索。此外，不良的早期生活经历与某些基因的等位基因相互作用，会通过表观遗传机制在整个生命过程中对大脑和身体产生持久影响。虽然预防最为重要，但大脑的可塑性为考虑脑体相互作用的治疗带来了希望。
