Steroid hormones and the brain: Linking “nature” and “nurture”

Contrary to earlier belief, the genetic constitution of each cell of the body (nature) is subject to modulation by environmental factors (nurture) which act throughout the life of the organism to shape the individual characteristics. The nervous system adapts and changes with the environment that the organism experiences through genomic activity controlled by chemical messengers from other nerve cells and from endocrine secretions. The nervous system expresses receptors for a number of circulating hormones, and the location of these hormone receptors has revealed a great deal about the neuroanatomy of neuroendocrine and behavioral control processes. The brain controls the endocrine system through the hypothalamus and pituitary gland, and it responds to circulating hormones throughout each stage of life. These effects begin during early development (eg., sexual differentiation of the brain; effects of maternal or neonatal stress). They continue in adult life in response to cyclic events (eg., season of year; time of day, controlling reproduction and daily activity-sleep rhythms of behavior); and they also include the behavior of other animals which alters hormone output. Hormones also operate during the aging process and under conditions which induce neural damage such as hypoxia and stress. This overview summarizes involvement of steroid hormones of gonads and adrenals in many of these processes and also examines the features of the genomic activity which is modified by these hormones. This area of research is fruitful because it brings together molecular, anatomical, physiological and behavioral approaches in an attempt to understand the longterm plasticity of the nervous system.This overview article, written in recognition of the contributions to neuroscience by Professor Holger Hydén, is based upon a Presidential Special Lecture delivered by the author at the Society for Neuroscience Meeting in Washington, D.C., on November 11, 1986     

Cholinesterases and cell proliferation in “nonstratified” and “stratified” cell aggregates from chicken retina and tectum

Summary Dissociated single cells from chicken retina or tectum kept in rotation-mediated cell culture aggregate, proliferate and establish a certain degree of histotypical cellto-cell relationships (sorting out), but these systems never form highly laminated aggregates (nonstratified R- and T-aggregates). In contrast, a mixture of retinal plus pigment epithelial cells forms highly stratified aggregates (RPE-aggregates, see Vollmer et al. 1984). The present comparative study of stratified and nonstratified aggregates enables us to investigate the process of cell proliferation uncoupled from that of tissue stratification. Here we try to relate these two basic neurogenetic processes with patterns of expression of cholinesterases (AChE, BChE) during formation of both types of aggregates.During early aggregate formation, in both stratified and nonstratified aggregates an increased butyrylcholinesterase activity is observed close to mitotically active cells. Quantitatively both phenomena show their maxima after 2–3 days in culture. In contrast, AChE-expression in all systems increases with incubation time. In nonproliferative areas, in the center of RPE-aggregates, the formation of plexiform layers is characterized initially by weak BChE and then strong AChE-activity. These areas correspond with the inner (IPL) and outer (OPL) plexiform layers of the retina in vivo. Although by sucrose gradient centrifugation we find that the 6S- and the fiber-associated 11S-molecules of AChE are present in all types of aggregates, during the culture period the ratio of 11S/6S-forms increases only in RPE-aggregates, which again indicates the advanced degree of differentiation within these aggregates.It is thus demonstrated that cholinesterases first correlate with neuronal cell proliferation and later with stratification, which indicates functions of both enzymes during both developmental periods.Abbreviations AChE acetylcholinesterase - BChE butyrylcholinesterase - iso-OMPA specific inhibitor of BChE - BW 284C51 specific inhibitor of AChE - IPL inner plexiform layer - OPL outer plexiform layer     

Against “Revolution” and “Evolution”

Those standard historiographic themes of evolution and revolution need replacing. They perpetuate mid-Victorian scientists history of science. Historians history of science does well to take in the long run from the Greek and Hebrew heritages on, and to work at avoiding misleading anachronism and teleology. As an alternative to the usual evo-revo themes, a historiography of origins and species, of cosmologies (including microcosmogonies and macrocosmogonies) and ontologies, is developed here. The advantages of such a historiography are illustrated by looking briefly at a number of transitions the transition from Greek and Hebrew doctrines to their integrations by medieval authors; the transition from the Platonist, Aristotelian, Christian Aquinas to the Newtonian Buffon and to the no less Newtonian Lamarck; the departures the early Darwin made away from Lamarcks and from Lyells views. Issues concerning historical thinking about nature, concerning essentialism and concerning classification are addressed in an attempt to challenge customary stereotypes. Questions about originality and influence are raised, especially concerning Darwins tree of life scheme. The broader historiography of Darwinian science as a social ideology, and as a worldview, is examined and the scope for revisions emphasised. Throughout, graduate students are encouraged to see this topic area not as worked out, but as full of opportunities for fresh contributions.     

Darwinian selection and “altruism”

Models are proposed for evolution at a single locus affecting altruistic behavior in which genotypic fitnesses are Darwinian and frequency (but not density) dependent. The fitnesses are composed, either in a multiplicative or an additive way, of factors which depend on the receipt and donation of altruistic behavior. The factors are determined from the matrices of conditional probabilities which describe the genotypes of relatives. Since selection occurs, these probabilities are in terms of genotype frequencies. The relationship between the risk to helper and benefit to recipient which allows altruism to evolve is shown to depend on the kinship coefficient between helper and helped, the particular fitness function proposed and the degree of dominance of the altruism. The commonly accepted criteria of W. D. Hamilton [J. Theor. Biol.7 (1964), 1–16, 17–52] apply only in the additive case. A second class of models of social cooperation independent of relationship and its evolutionary dynamics are discussed.     

GABA and “neuro-cardiovascular” mechanisms

One has only to recall that GABA appears to be a major inhibitory neurotransmitter in the vertebrate central nervous system (CNS), that it exerts a hypotensive action upon systemic administration, that it is present in the blood, that its actions are antagonized by bicuculline and picrotoxin and facilitated by benzodiazepines, and that receptors for GABA exist in cerebral blood vessels, to consider that GABA is somehow involved in cardiovascular regulation. One might even postulate that influences upon GABA-ergic mechanisms are involved in that dangerous sequence of biological activities: environmental stress → anxiety → atherosclerosis and hypertension, the latter of which represent major health problems of man. Herein, some evidence that appears to support this view will be presented.     

“Sunbursts” and “christiesomes”: Cellular fragments in normal cow and goat milk

Summary Goats' milk includes numerous cell fragments (christiesomes) which originate from the mammary secretory cells, contain well preserved endoplasmic reticulum, mitochondria and lipid droplets, and are responsible for the considerable triglyceride synthesising capacity of fresh goat milk. Cows' milk shows a few such particles only after repeated oxytocin-aided milkings. Cows' milk does contain quite different particles which have a dense content with a few small vesicles and numerous microvillus-like protrusions on one side (sunbursts). These have not been found in goats milk. Cytoplasmic particles similar to sunbursts have been found on the surface of the mammary secretory epithelium. It is suggested that they are residues of dead cells.     

The “survivor effect” and the evolution of parthenogenesis and self-fertilization

Parthenogenetic or self-fertilizing species are often reduced to small numbers of survivors or colonists. These types of reproduction may therefore evolve because they eliminate problems of finding a mate. It is argued here that outbreeding populations which are often reduced to a few survivors will experience heavy offspring losses when population expansion occurs. This ‘survivor effect’ results from the production of many individuals homozygous for deleterious mutations (i.e. inbreeding depression). Parthenogenetic and selfing species do not experience a “survivor effect”. This effect together with mate-finding problems will tend to cause the evolution of parthenogenesis and selfing in weedy or colonizing species.     

Psychoanalysis and cycles of “subversion” in modern art and anthropology

Frances M. Slaney is Professor of Anthropology at the University of Laval, Quebec.     

Similarities and differences between “uncapped” telomeres and DNA double-strand breaks

Telomeric DNA is present at the ends of eukaryotic chromosomes and is bound by telomere “capping” proteins, which are the (Cdc13–Stn1–Ten1) CST complex, Ku (Yku70–Yku80), and Rap1–Rif1–Rif2 in budding yeast. Inactivation of any of these complexes causes telomere “uncapping,” stimulating a DNA damage response (DDR) that frequently involves resection of telomeric DNA and stimulates cell cycle arrest. This is presumed to occur because telomeres resemble one half of a DNA double-strand break (DSB). In this review, we outline the DDR that occurs at DSBs and compare it to the DDR occurring at uncapped telomeres, in both budding yeast and metazoans. We give particular attention to the resection of DSBs in budding yeast by Mre11–Xrs2–Rad50 (MRX), Sgs1/Dna2, and Exo1 and compare their roles at DSBs and uncapped telomeres. We also discuss how resection uncapped telomeres in budding yeast is promoted by the by 9–1–1 complex (Rad17–Mec3–Ddc1), to illustrate how analysis of uncapped telomeres can serve as a model for the DDR elsewhere in the genome. Finally, we discuss the role of the helicase Pif1 and its requirement for resection of uncapped telomeres, but not DSBs. Pif1 has roles in DNA replication and mammalian and plant CST complexes have been identified and have roles in global genome replication. Based on these observations, we suggest that while the DDR at uncapped telomeres is partially due to their resemblance to a DSB, it may also be partially due to defective DNA replication. Specifically, we propose that the budding yeast CST complex has dual roles to inhibit a DSB-like DDR initiated by Exo1 and a replication-associated DDR initiated by Pif1. If true, this would suggest that the mammalian CST complex inhibits a Pif1-dependent DDR.     

Differential expression of “Fe-repressible” and “growth-rate-sensitive” proteins in Neisseria meningitidis and Neisseria gonorrhoeae

By varying growth conditions, we were able to differentiate (SDS-PAGE) between true Fe-repressible proteins and growth-rate-sensitive proteins (GSP's) (60-110 Kd) in outer membranes of iron-starved meningococci and gonococci. Immunological characterization with monoclonal antibodies raised against the GSP's revealed (GIRA) crossreactivity between different GSP's. On the basis of common epitopes, two groups of proteins could be distinguished. Immuno-electron-microscopy showed that proteins of both groups were exposed at the cell surface.     

“Theory” in Theory and Practice

A central obstacle to accepting evolution, both among students and the general public, is the idea that evolution is “just a theory,” where “theory” is understood in a pejorative sense as something conjectural or speculative. Although scientists and textbooks constantly explain that the scientific use of “theory” is quite different, the pejorative use continues to cause confusion, in part because of its deep roots in a popular, Baconian, understanding of science. A constructivist approach, whereby students are helped to examine the adequacy of their preconceptions about “theory” for themselves and to revise or replace them appropriately, is recommended.     

Organization and expression of polygalacturonase and other ripening related genes in Ailsa Craig “Neverripe” and “Ripening inhibitor” tomato mutants

The organization and expression of ripening-related genes were investigated in normal tomato (Lycopersicon esculentum cv. Ailsa Craig) and in Neverripe (Nr) and Ripening inhibitor (rin) mutants.Hybridization studies with ripening-related cDNA clones showed that the gene for polygalacturonase (PG) is barely expressed in rin and expressed at a low level in Nr fruit. Four other genes were found to be expressed at reduced levels in rin. Exogenous ethylene was able to restore higher levels of expression of all the genes showing reduced expression in rin except that for PG. However, exogenous ethylene did not restore normal ripening in rin fruit. Analysis of chromosomal DNA by Southern blotting indicated that all the genes studied, including the PG gene, and also an upstream promoter of the PG gene, are present in the rin and Nr genomes and appear to be arranged in a similar way to those in normal tomatoes. The results are discussed in the light of the suggestion that these mutations may involve part of the regulatory apparatus leading to the expression of ripening genes such as PG.