A.J.H. de Ruiter

Neuroendocrine states and behavioral and physiological stress responses.

Publisher Summary This chapter presents a novel, behavioral physiological stress concept that originates from the classical view that stress is a response. This new concept is extended to environment, behavior, and physiology, and it incorporates the novel neuroendocrine views including the neuropeptide concept. Stress is viewed as a general biological and usually functional response to environmental and bodily demands. A stress depends on interactions among environment, individual characteristics and the properties of stressors, stress, and the physiological systems, and also among the nervous system, peripheral organ systems, and the neuroendocrine system. To adapt to the altering social and physical environmental demands, man and other animals require a chain of behavioral, neuroendocrine, and autonomic physiological and metabolic responses to maintain bodily and mental homeostasis. The neuroendocrine state of the brain is given a central position in determining the state of health or disease of mind and body.

Differential Lateral Septal Vasopressin Innervation in Aggressive and Nonaggressive Male Mice

The vasopressinergic (VP) projection from the bed nucleus of the stria terminalis (BNST) to the lateral septum (LS) is sexually dimorphic and dependent of androgens at adult and neonatal age. We studied the relation between testosterone (T) and VP in male mice, which were genetically selected for their differences in aggression level. Aggressive males, characterized by a short attack latency (SAL), have a higher production capacity of T at adult age compared to males with a long attack latency (LAL). Neonatally, however, a higher T production occurs in the nonaggressive LAL males than in SAL males. In the present study we showed a more dense VP-immunoreactive (VP-ir) innervation in the LS and a higher VP-ir neuron density in the BNST of LAL males as compared to SAL males. The described differences may be the consequence of a differential neonatal androgen effect on the organization of the forebrain vasopressinergic network.

Coping with stress in rats and mice: Differential peptidergic modulation of the amygdala-lateral septum complex

This chapter focuses on the parvicellular vasopressin (VP) system originating from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number of limbic brain areas including the septum-hippocampal complex. Interestingly, this VP system is sexually dimorphic and the VP synthesis in this system depends on circulating gonadal steroids. Studies in rats and mice show that the variation in the lateral septal VP network within the male gender is as large as the variation between the sexes as reported in the literature. Non-aggressive males are characterized by a far more extensive VP network and a higher VP content in the lateral septal area than aggressive males. A review of the literature on the function of lateral septal VP in the organization of behavior reveals not only a modulatory role of behavior in a social context, but also of fear- and anxiety-related behaviors. It is argued that these seemingly diverse functions might be explained by the concept of coping style. Extensive behavioral and physiological analyses in a variety of animal species show that males may be characterized by the way in which they cope with environmental challenges in general. Aggressive males tend to cope actively with their environment whereas non-aggressive males seem to accept the situation as it is more easily. In several tests, we determined the effects of chronic infusion of the V1 receptor antagonist locally into the lateral septal area in male rats. The main conclusion from these experiments is that LS VP does not modulate coping style in general. However, the experiments confirm the idea that LS VP has a certain degree of functional specificity in social behavior and social learning tasks. Together with the observation that the size and distribution of the vasopressinergic system may be highly variable between individual males in relation to their coping style, this suggests that the lateral septal vasopressinergic system is involved in the differential capacity of individuals to cope behaviorally with challenges of a social nature.

Differential lateral septal vasopressin in wild-type rats : Correlation with aggression

The vasopressin (VP)-containing projections from the cells of the bed nucleus of the stria terminalis to the lateral septum (LS) are sexually dimorphic and dependent on gonadal steroids. Recently, the difference in VP distribution found among both sexes was also demonstrated in male mice genetically selected for different levels of intermale aggression. In the present study we examined whether this differential VP distribution in males also exists in an outbred strain of wild-type rats. After the animals were tested for their level of aggression, the VP content and the fiber density of the LS were measured using radioimmunoassay and immunocytochemistry, respectively. In addition, basal levels of plasma testosterone (T) were measured. Both biochemical data and immunocytochemical data revealed a negative correlation between VP and intermale aggression. Aggressive rats exhibited low levels of VP whereas intermediate and nonaggressive animals showed higher levels. Differences in adult levels of T were not found. The results are in accordance with the observations previously found in male mice, reconfirming the correlation between lateral septal VP and aggression.

Aggression in Wild House Mice: Current State of Affairs

This paper reviews our present state of knowledge of genetic variation in (offensive) aggression in wild house mice. The basic tools in this research were lines bidirectionally selected for attack latency (fast attacking SAL and slow attacking LAL males), descended from a feral population. Using congenic lines for the nonpseudoautosomal region of the Y chromosome (YNPAR), reciprocal crosses between (parental) SAL and LAL, and crosses between parentals and congenics, an autosomally dependent Y chromosomal effect on aggression has been found. Both the pseudoautosomal (YPAR) region and the YNPAR play a role. As for environmental sources of variation, prenatal and postnatal maternal effects are of minor importance for the development of aggression differences. One of the physiological factors by which genetic effects may be mediated is testosterone (T). Besides quantitative aspects, the timing of T release seems crucial. Two important time frames are discussed: the perinatal and pubertal time periods. Finally, neurochemical and neuroanatomical correlates are considered. Differences in neostriatal dopaminergic activity, and sizes of the intra- and infrapyramidal mossy fiber terminal fields, as well as Y chromosomal effects on the latter two, are discussed.

Testosterone-dependent transformation of nephronic tubule cells into serous and mucous gland cells in stickleback kidneys in vivo and in vitro

When male sticklebacks come into breeding condition, the cells of the second proximal segments and collecting tubules of the nephrons are transformed into cells producing secretions used for nest building. This investigation is aimed at determining whether this transformation of renal tubule cells is induced directly by androgens. To this end, renal tissue is cultured with androgen supplement, either methyltestosterone or 11-ketotestosterone. The results are compared with the effects of methyltestosterone on the tubule cells in castrated males. In the nephronic tubules of methyltestosterone-treated fish, the basal labyrinth—and thus most of the ion reabsorbing capacity of the tubules—disappears within 4 days, probably as a result of autophagous digestion. During this period the cells become considerably enlarged and an extensive granular endoplasmic reticulum develops. The Golgi apparatus proliferates and starts to form secretory granules. In renal tissue cultured for 10 days with methyltestosterone, secretory granules are observed in the second proximal tubule cells, but no secretory activity can be detected in the collecting tubules. After 5 days in cultures supplemented with 11-ketotestosterone, however, signs of secretory activity are apparent already in the second proximal tubules, and to a lesser extent, in the collecting tubules. After 10 days of incubation with 11-ketotestosterone, glandular transformation is almost completed. The results provide strong evidence that the transformation of nephronic tubule cells into mucus-secreting cells in sexually mature sticklebacks is due to a direct effect of androgen. It can be concluded then that, at least in vitro, 11-ketotestosterone may be considered more androgenic than methyltestosterone.

The effect of prolactin on fanning behavior in the male three-spined stickleback, Gasterosteus aculeatus L

The effect of administration of homologous prolactin on fanning behavior, an important aspect of parental care in sticklebacks and many other teleost fish, was studied. Prolactin was administered by implantation of an additional pituitary prolactin lobe in the dorsal body musculature of males with a nest without eggs. The low but rather constant level of fanning behavior is significantly increased from Day 6 to Day 12 after administration of the prolactin lobe. The implantation has no noticeable effects on cell and nuclear size or on the ultrastructure of the in situ prolactin cells of the recipient fish. Recovered prolactin lobe implants show two categories of prolactin cells. The major category consists of cells that are well developed and, similar to in situ prolactin cells, show structural signs of high secretory activity. The other prolactin cell category in the implants shows signs of cellular involution. Ten days after implantation, the first category predominates, and 16 days after implantation the second category. Prolactin lobe implantation increases the number of mucocytes in the epithelium of the skin, in particular at Day 10, and to a lesser extent at Day 16. This is considered evidence for a transient rise in blood prolactin levels in the recipient fish. We conclude that prolactin stimulates fanning behavior in male sticklebacks.

Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny

Testosterone (T) and estradiol (E2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behaviour via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E2, by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E2 on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of males fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant differences between embryonic days or a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aromatase Activity in the Preoptic Area Differs Between Aggressive and Nonaggressive Male House Mice

Treatment with testosterone (T) or estradiol (E2) facilitates intraspecific aggressive behavior in adult rodents. Brain aromatization of T to E2 appears to be involved in facilitation of fighting behavior. In the present study we measure the in vitro brain aromatase activity (AA) in the preoptic area (POA), amygdaloid nuclei (Am), ventromedial hypothalamus (VMH), and parietal cortex (CTX) from two strains of adult male house mice, which were genetically selected for territorial aggression, based upon their attack latencies (short attack latency: SAL; long attack latency: LAL). The results reveal a higher AA in the POA of nonaggressive LAL males, as compared to aggressive SAL animals. The POA AA is, thus, inversely correlated with aggressiveness. The AA levels in both the VMH and Am do not differ significantly between strains. Furthermore, a differential brain area-specific AA distribution exists: POA > VMH AA in LAL, whereas POA < VMH in SAL. In both selection lines, the Am exhibits the highest levels of AA, as compared to the other investigated areas. Kinetic studies revealed that the aromatase Km is similar in both strains. The results indicate that the strain difference in AA is specific to the POA, but is not necessarily positively correlated with circulating plasma T levels. Other factors, in addition to androgen, are probably involved in the regulation of POA aromatase. We suggest that a higher neural androgen receptor sensitivity exists in the POA of nonaggressive LAL males, resulting in higher adult POA AA, despite lower concentrations of circulating T.

Changes in glomerular structure after sexual maturation and seawater adaptation in males of the euryhaline teleost Gasterosteus aculeatus L.

SummaryIn sexually mature male sticklebacks, the renal tubular cells are transformed from ion reabsorbing to mucus secreting cells and in these fish concomitant changes take place in the glomeruli.The present study compares glomerular structure of immature males in fresh water (controls) to those of mature males in fresh water and to immature male sticklebacks in seawater. Glomerular structure is markedly altered in the latter two groups and the changes are similar to a large extent. In these two groups the renal capsules and glomeruli are smaller and the lumina of the glomerular capillaries decrease in diameter, while the number and size of the endothelial fenestrations are reduced. Mesangial cells proliferate and the mesangial matrix greatly expands in both the centrolobular region and the subendothelial space around the capillaries. The secretory activity of the podocytes is enhanced and is responsible for the observed increase in thickness of the outer layer of the basal lamina, the lamina rara externa. The area covered by the filtration slit membranes is reduced, probably as a consequence of fusion of the pedicels of the podocytes. The permeability characteristics of the glomerular filtration barrier for macromolecules, as studied with ferritin injections, remain unaltered. However, the observed differences point to a reduction of the glomerular filtration rate (GFR) during maturation in male sticklebacks, as well as during adaptation of sticklebacks to seawater. This conclusion is in line with physiological evidence.