Neurotoxicity of Glucocorticoids in the Primate Brain

Severe and prolonged physical and psychological stress is known to cause brain damage; long-term torture victims in prison bare later developed psychiatric disorders and cerebral cortical atrophy observed in CT scans (Jensen, Genefke, Hyldebrandt, Pedersen, Petersen, and Weile. 1982). In nonhuman primates, we observed degeneration and depletion of the hippocampal neurons in African green monkeys that had been severely abused by cagemates and died with complications of multiple gastric ulcers and adrenal cortical hyperplasia (Uno, Tarara, Else, Suleman and Sapolsky, 1989). In our previous studies the administration of dexamethasone (DEX) (5 mg/kg) to pregnant rhesus monkeys at 132 to 133 days of gestation induced degeneration and depletion of the hippocampal pyramidal and dentate granular neurons in the brains of 135-gestation-day fetuses, and these changes were retained in the brains of fetuses at near term, 165 days of gestation (Uno, Lohmiller, Thieme, Kemnitz, Engle, Roecker, and Farrell, 1990). We also found that implantation of a cortisol pellet in the vicinity of the hippocampus in adult vervet monkeys induced degeneration of the CA3 pyramidal neurons and their dendritic branches (Sapolsky, Uno, Rebert, and Finch, 1990). Thus, hippocampal pyramidal neurons containing a high concentration of glucocorticoid receptors appear to be highly vulnerable to either hypercortisolemia caused by severe stress or to exposure to exogenous glucocorticoids. To study the long-term postnatal sequelae of prenatal brain damage, eight rhesus monkeys were treated with either DEX (5 mg/kg), 5 animals, or vehicle, 3 animals, at 132 to 133 days of gestation. After natural birth, all animals lived with their mothers for 1 year. At 9 months of age, we found that DEX-treated animals had significantly high plasma cortisol at both base and post stress (isolation) levels compared to age-matched vehicle-treated animals. Magnetic resonance images (MRI) of the brain at 20 months of age showed an approximately 30% reduction in size and segmental volumes of the hippocampus in DEX-treated compared to vehicle-treated animals. Measurements of whole brain volume by MRI showed no significant differences between DEX and vehicle groups. Prenatal administration of a potent glucocorticoid (DEX) induced an irreversible deficiency of the hippocampal neurons and high plasma cortisol at the circadian baseline and post-stress levels in juvenile rhesus monkeys. These results suggest that the hippocampus mediates negative feedback of cortisol release; a lack or deficiency of the hippocampal neurons attenuates this feedback resulting in hypercortisolemia. The hippocampal deficiency in rhesus monkeys induced by prenatal administration of DEX appears to be a good model for neuroendocrinological dysfunctions and hippocampal development in human juveniles whose mothers were exposed to severe stress or received a high dose of glucocorticosteroids during pregnancy.     

Fungal conservation in Scotland: Recent progress and future priorities

Summary

In recent years, fungal conservation in Scotland has made substantial progress, particularly as a result of field surveys undertaken in support of the Biodiversity Action Plans developed for selected species. Results are presented from four recent surveys: (i) fungal diversity in conifer plantations, (ii) hydnoid (‘tooth’) fungi in coniferous forests, (iii) grassland fungi, (iv) fungal survey of the Mar Lodge Estate. These surveys have substantially improved knowledge of the conservation status of a number of threatened taxa, and have also provided insights into patterns of fungal diversity at a range of scales. The results indicate that some of the fungal communities of Scotland, such as those associated with unimproved grasslands, are of international conservation importance. The implications of the survey results for conservation management are discussed, and suggestions are made regarding priorities for future work. In particular, there is a need to provide conservation managers with guidance on how fungal conservation can be achieved in practice.     

From bridewealth to dowry?

Significant amounts of wealth have been exchanged as part of marriage settlements throughout history. Although various models have been proposed for interpreting these practices, their development over time has not been investigated systematically. In this paper we use a Bayesian MCMC phylogenetic comparative approach to reconstruct the evolution of two forms of wealth transfers at marriage, dowry and bridewealth, for 51 Indo-European cultural groups. Results indicate that dowry is more likely to have been the ancestral practice, and that a minimum of four changes to bridewealth is necessary to explain the observed distribution of the two states across the cultural groups. A preliminary version of this paper was presented at the 16^th meeting of the Human Behavior and Evolution Society (HBES), Berlin 2004. Mark Pagel and Andrew Meade provided the software, the coded linguistic data, and valuable advice on their use. LF is funded by Fondazione Ing. Aldo Gini (Italy), the ESRC (UK), and the UCL Graduate School (UK). Five anonymous reviewers provided helpful comments. The authors are based at the Department of Anthropology of UCL and members of the AHRC Centre for the Evolutionary Analysis of Cultural Behaviour (CEACB). LF is studying towards a PhD, CH is a CEACB Senior Research Fellow, and RM is Professor of Evolutionary Anthropology.     

Human DNA topoisomerase II: evaluation of enzyme activity in normal and neoplastic tissues

We have used both a quantitative filter binding assay and a decatenation assay to measure DNA topoisomerase II activity. The filter binding assay, which measures catenating activity, is able to detect topoisomerase II activity at 50-100-fold lower protein concentrations than the decatenation assay. Because of this remarkable sensitivity, we have been able to quantitate topoisomerase II activity in a variety of normal and neoplastic human tissues. The highest level of enzyme activity in normal tissues was found in the spleen and thymus. The highest level of enzyme activity in neoplasms was found in those that clinically behave in an aggressive manner and had a high proliferative status by flow cytometry. Surprisingly, these high topoisomerase II values in the neoplastic specimens are in the same range of values found in normal nonproliferating tissue. Since much previous data indicate that the enzyme is apparently a property of only proliferating cells, this finding might suggest that human tissues contain more than one form of the enzyme. The finding that 35-65% of the topoisomerase II activity in human tissues is resistant to teniposide suggests that more than one enzyme form exists.