Social status differentiates rapid neuroendocrine responses to restraint stress

Male Anolis carolinensis that win aggressive interactions mobilize neuroendocrine responses to social stress more rapidly than defeated lizards. We initially examined temporal patterns of neuroendocrine response to restraint stress in lizards of unknown status, and then investigated whether winning males respond more rapidly to this non-social stressor. Size-matched male pairs interacted to establish social status, and then were returned to individual home cages for 3 days. Plasma and brains were collected from non-restrained dominants and subordinates, and from a non-interacting control group. Additional groups of dominants and subordinates underwent 90 s restraint stress, with plasma and brains collected either immediately or 300 s after restraint. In lizards of unknown social status restraint stimulated rapid monoaminergic responses in nucleus accumbens, hippocampus, amygdala, and locus ceruleus, with delayed responses seen in VTA and raphé. Non-restrained dominants and subordinates had lower levels of raphé serotonergic activity and lower hippocampal dopaminergic activity 3 days after interacting, compared to controls. Dominants had higher corticosterone levels, both immediately and 300 s after restraint, than either non-restrained dominants or restrained subordinates. Restraint induced higher raphé serotonergic activity in dominants. However, subordinates also showed rapid responses to restraint; exhibiting lower hippocampal dopamine (DA) levels than non-restrained subordinates. At 300 s after the stress, amygdalar serotonin levels increased in dominants, while subordinates showed higher amygdalar DA levels. These results suggest that stressful aggressive interactions will not only alter basal neurochemical activity, but also influence neuroendocrine responses to non-social stressors according to individual social status.     

Evaluation of nutritional status

The assessment of nutritional status has become very popular, especially for patients undergoing stress (surgery) or potential parenteral nutrition. Evaluation of cancer patients is essentially the same as for other patients. Body fat reserves are approximated by subcutaneous skinfold measurements. Somatic protein (skeletal muscle) mass is decreased in marasmus (protein-calorie malnutrition) and is evaluated by anthropometric determinations, based upon age and sex or both. Instead of using relatively inadequate standards such as the 1959 Metropolitan Life Insurance tables for ideal weight, it is advocated to use the population percentiles derived from the Health and Nutritional Examination Survey (HANES) published in 1979. The visceral protein mass is decreased in kwashiorkor and is approximated by study of the liver transport proteins. A mixed-type of protein-calorie malnutrition may exist, e.g., cancer cachexia, with marked decrease of immunocompetence. A prognostic nutritional index, based on biologic measurements rather than true nutritional assessment, can predict the probability of complications and survival in severely ill patients. All such studies should be used to substantiate good clinical judgement, based on adequate history and physical examination with emphasis on the nutritional aspects.     

Differential blood count and activity of lymphocytic dehydrogenases in rats with genetically different neuroendocrine status

Differential blood count and activity of lymphocytic dehydrogenases are studied in rats genetically liable to catalepsy and in Wistar rats. The activity of lymphocytic dehydrogenases is decreased, sex differences in activities of the studied enzymes leveled, and absolute counts of peripheral blood lymphocytes are decreased in rats liable to catalepsy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 5, pp. 555–557, May, 1998     

Opponent recognition and social status differentiate rapid neuroendocrine responses to social challenge

Individual social status discriminates rapid neuroendocrine responses to non-social stress in male Anolis carolinensis, but whether such status-influenced reactions are retained in response to subsequent social stress is unknown. Dominant and subordinate males modify their behavioral responses to social challenge according to familiarity of the opponent, suggesting that accompanying neuroendocrine responses may differ according to opponent recognition despite social rank. We examined endocrine and neurochemical correlates of prior social status and opponent recognition during the opening stages of social challenge. Male pairs interacted and established dominant/subordinate status, followed by 3 days separation. Subsequently, subjects were paired with either the same opponent or an unfamiliar male according to rank (dominant with subordinate). After 90 s of social exposure, subjects were caught and brains and plasma collected for measurement of circulating corticosterone and limbic monoamines. Controls included pairs experiencing just one 90 s encounter plus a group of non-interacting subjects. Opponent recognition differentiated status-influenced responses, such that dominant lizards paired with familiar subordinate opponents had increased hippocampal dopamine and epinephrine, but showed increased plasma corticosterone and ventral tegmental area (VTA) norepinephrine when challenged with an unfamiliar opponent. Subordinate lizards encountering familiar opponents also had increased corticosterone, along with decreased hippocampal dopamine and increased VTA epinephrine, but showed no changes in response to an unfamiliar opponent. Such plasticity in status-influenced rapid neuroendocrine responses according to opponent recognition may be necessary for facilitating production of behavioral responses adaptive for particular social contexts, such as encountering a novel versus familiar opponent.     

Evaluation of longevity enhancing compounds against transactive response DNA-binding protein-43 neuronal toxicity

In simple systems, lifespan can be extended by various methods including dietary restriction, mutations in the insulin/insulin-like growth factor (IGF) pathway or mitochondria among other processes. It is widely held that the mechanisms that extend lifespan may be adapted for diminishing age-associated pathologies. We tested whether a number of compounds reported to extend lifespan in C. elegans could reduce age-dependent toxicity caused by mutant TAR DNA-binding protein-43 in C. elegans motor neurons. Only half of the compounds tested show protective properties against neurodegeneration, suggesting that extended lifespan is not a strong predictor for neuroprotective properties. We report here that resveratrol, rolipram, reserpine, trolox, propyl gallate, and ethosuximide protect against mutant TAR DNA-binding protein-43 neuronal toxicity. Finally, of all the compounds tested, only resveratrol required daf-16 and sir-2.1 for protection, and ethosuximide showed dependence on daf-16 for its activity.     

Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval

BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.     

Hormonal regulation of longevity in mammals

Multiple biological and environmental factors impact the life span of an organism. The endocrine system is a highly integrated physiological system in mammals that regulates metabolism, growth, reproduction, and response to stress, among other functions. As such, this pervasive entity has a major influence on aging and longevity. The growth hormone, insulin-like growth factor-1 and insulin pathways have been at the forefront of hormonal control of aging research in the last few years. Other hormones, including those from the thyroid and reproductive system have also been studied in terms of life span regulation. The relevance of these hormones to human longevity remains to be established, however the evidence from other species including yeast, nematodes, and flies suggest that evolutionarily well-conserved mechanisms are at play and the endocrine system is a key determinant.     

Inheritance of human longevity in Iceland

The idea that human longevity is influenced by genetic factors has recently received strong support from work on other species. On the basis of partial population studies and selected kinships, significant correlations between the ages of parents and offspring have been reported, and some but not all twin studies have confirmed that human longevity is moderately inherited. However, studies based upon a relatively small proportion of a population are susceptible to sampling error and selection bias. Here we report the use of a comprehensive population-based computerised genealogy database to examine multigenerational relationships among those who live to the 95th percentile in Iceland. We have developed a clustering tool which can generate large extended pedigrees connecting individuals from any list using the genealogy database. First degree relatives of those living to the 95th percentile are almost twice as likely to live to the 95th percentile compared with controls. Furthermore, we have developed an algorithm which we have named the Minimum Founder Test (MFT) to examine the degree of relatedness of any population-based list of individuals to estimate whether a trait has a familial component. The data indicate that there is a significant genetic component to longevity. In addition, age-specific death rates are significantly lower in the offspring of long-lived parents compared with controls, especially after age 70.     

Mechanisms of neuroendocrine differentiation in pulmonary neuroendocrine cells and small cell carcinoma

We review the significance of a network of proneural basic helix-loop-helix (bHLH) factors. Immunohistochemically, pulmonary neuroendocrine cells (PNECs) are positive for Mash1, one of the activator bHLHs, and non-PNECs such as Clara cells are positive for Hes1, one of the repressor bHLHs. Since mice deficient for the Mash1 gene do not possess PNEC and mice deficient for the Hes1 gene have many PNECs, it is suggested that a network of bHLHs work in cell fate determination of lung epithelium. Moreover, the Notch pathway could play a role in cell differentiation mechanisms in the lung because this signaling pathway has been reported to work in various tissues. PNECs have been reported to modulate various nonneoplastic human lung diseases. We demonstrate that PNECs in usual interstitial pneumonia and hASH1 (human homolog of Mash1) are upregulated in diseased lung tissues. Moreover, studies of small cell carcinoma and non-small cell carcinoma suggest that neuroendocrine differentiation could be regulated by hASH1. In non-small cell carcinoma, Hes1 and Notch signaling may have roles in maintaining cell differentiation. Thus, a network of bHLHs and Notch signaling are important in cell differentiation of normal and pathologic lung epithelial cells.     

Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.     

Familial transmission of longevity

The Tau model of phenotypic transmission has been used to analyze the familial correlations (nuclear families and extended families) of longevity at Arthez d'Asson (individuals born between 1686 and 1899). At birth, the transmissibility (t2) is very weak: 0.103; at 20 years old, t2 = 0.167; at 50 years old, t2 = 0.294. The effect of sibling environment on children's phenotype is s = 0.086 at birth, is thus null. A cohabitional effect between spouses: p = 0.167 appears after 50 years. There is no social homogamy effect via grandparents.     

Familial transmission of longevity

The Tau model of phenotypic transmission has been used to analyze the familial correlations (nuclear families and extended families) of longevity at Arthez d'Asson (individuals born between 1686 and 1899). At birth, the transmissibility (t²) is very weak: 0·103; at 20 years old, t² = 0·167; at 50 years old, t² = 0·294. The effect of sibling environment on children's phenotype is s = 0·086 at birth, is thus null. A cohabitional effect between spouses: p = 0·167 appears after 50 years. There is no social homogamy effect via grandparents.     

Exercise and longevity

Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to “successful aging”. In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population.     

HLA and longevity

One hundred fifty-five healthy nonagenarians, 55 men and 100 women, all French Caucasians, were phenotyped for alleles of the A, B, C, DR loci of the HLA complex. The observed HLA antigen frequencies were compared to those of a control series of 133 males and 179 females whose ages ranged from 10 to 50 years. When comparing the total young and elderly series, no significant differences were observed with respect to HLA antigen distribution or heterozygosity at any of the loci. When taking sex difference into account, however, an excess of the Cw1 antigen was found in the group of elderly females (p < 0.001) and an excess of the Cw7 antigen in the group of elderly males (p < 0.001). Of particular significance was the fact that Cw7 belonged in this instance to a phenotypic combination (and most probably to the corresponding haplotype) A1/Cw7/B8/DR3 which was found significantly increased in male nonagenarians (p < 0.001). These results support the hypothesis that certain HLA haplotypes are associated with survival advantage.     

Exercise and longevity

Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to “successful aging”. In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population.