Rockefeller University

About: Rockefeller University is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 15867 authors who have published 32938 publications receiving 2940261 citations. The organization is also known as: Rockefeller University & Rockefeller Institute.

Protective and damaging effects of mediators of stress. Elaborating and testing the concepts of allostasis and allostatic load.

Abstract: Stress is a condition of human existence and a factor in the expression of disease. A broader view of stress is that it is not just the dramatic stressful events that exact their toll but rather the many events of daily life that elevate activities of physiological systems to cause some measure of wear and tear. We call this wear and tear "allostatic load," and it reflects not only the impact of life experiences but also of genetic load; individual habits reflecting items such as diet, exercise, and substance abuse; and developmental experiences that set life-long patterns of behavior and physiological reactivity (see McEwen). Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation, but in the long run allostatic load causes changes in the body that lead to disease. This will be illustrated for the immune system and brain. Among the most potent of stressors are those arising from competitive interactions between animals of the same species, leading to the formation of dominance hierarchies. Psychosocial stress of this type not only impairs cognitive function of lower ranking animals, but it can also promote disease (e.g. atherosclerosis) among those vying for the dominant position. Social ordering in human society is also associated with gradients of disease, with an increasing frequency of mortality and morbidity as one descends the scale of socioeconomic status that reflects both income and education. Although the causes of these gradients of health are very complex, they are likely to reflect, with increasing frequency at the lower end of the scale, the cumulative burden of coping with limited resources and negative life events and the allostatic load that this burden places on the physiological systems involved in coping and adaptation.

Estrogen actions in the central nervous system.

Abstract: I. Introduction II. Mechanisms of Estrogen Action A. “Genomic” and “nongenomic” mechanisms B. Steroid hormone actions on gene expression C. Subtypes of estrogen receptors D. Steroid hormone actions on putative receptors on membranes E. Rapid actions of steroids on neuronal excitability F. Steroid hormone actions via second messengers G. Neuroprotective effects of estrogens H. Summary III. Areas of the Brain Affected Outside of the Hypothalamus A. Studies of hypothalamic and extrahypothalamic actions of estrogens B. Estrogens and the cholinergic system C. Estrogens and the serotonergic system D. Catecholaminergic neurons E. Spinal cord F. Hippocampus G. Glial cells, endothelial cells, and the blood-brain barrier H. Summary IV. Effects of Estrogens on Learning and Memory V. Estrogens, Neuroprotection, and Alzheimer’s Disease VI. Conclusions

Atlas of estradiol-concentrating cells in the central nervous system of the female rat.

Abstract: Two hours following intraperitoneal injection, estradiol-H3 is concentrated by cells in a system of limbic and hypothalamic structures. Preoptic-hypothalamic nuclei containing estrogen-concentrating cells include the medial preoptic area, medial anterior hypothalamus, ventromedial nucleus, arcuate nucleus and ventral premammillary nucleus. Limbic structures include the medial and cortical nuclei of the amygdala, lateral septum, bed nucleus of the stria terminalis, diagonal band of Broca, olfactory tubercle, ventral hippocampus, and prepiriform and entorhinal cortex. Labelled cells were also found in the lateral and ventrolateral portions of the mesencephalic central grey. Compared to these regions, most other regions of the nervous system, including the spinal cord, have very small numbers of labelled cells, which are relatively weakly labelled, and are not found in regular, specific locations. The distribution of estrogen-concentrating cells determined with the present autoradiographic method agrees with previous autoradiographic conclusions and with biochemical results from cell fractionation experiments. The locations of estrogen-concentrating cells coincide in several brain regions with locations of estrogen-dependent neuroendocrine control mechanisms, as determined by brain implants, lesions, electrical stimulation, and electrophysiological recording. Moreover, experimental neuroanatomical studies have provided evidence for several pathways connecting regions which concentrate radioactive estradiol. Taken together, the evidence suggests a limbic-hypothalamic system of estrogen-concentrating neurons which participate in the control of mating behavior and of gonadotrophin release from the pituitary.

Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells.

Abstract: Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4(+) and CD8(+) T cells. Cross-presentation of antigens to CD8(+) T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.