Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term survival of spinal motoneurons

Activation of courtship behavior in male red-sided garter snakes is independent of androgens. Only exposure to extended periods of low temperature with subsequent warming stimulates courtship in males. The pineal gland is thought to transduce temperature as well as photoperiodic information in reptiles. Therefore, we explored the relationship of the pineal and melatonin to sexual behavior in this species. Pinealectomy of male garter snakes disrupted sexual behavior upon emergence from a 17-week period of low temperature in approximately 60% of treated individuals in each of the 3 years of study. However, 40% of the males were unaffected by the pinealectomy, engaging in vigorous courtship. Administration of exogenous, chronic melatonin did not significantly modulate the effect of pinealectomy. Upon pinealectomy in the autumn (before hibernation), plasma levels of melatonin fell. However, upon emergence from hibernation, melatonin levels in pinealectomized (PINX) and sham-treated (SHAM) animals were equivalent, indicating extrapineal source(s) of melatonin. However, PINX males did not exhibit a diel cycle in melatonin levels upon emergence. Instead, melatonin remained elevated through the subsequent 24-hr period. SHAMs did exhibit a diel cycle. Ten days after emergence, PINX animals either had a disrupted/abnormal melatonin cycle and were non-courters or had a cycle similar to SHAM males and courted. Therefore, a normal diel cycle of melatonin appeared necessary for the proper expression of courtship behavior. These results suggest that the pineal in snakes 1) is part of a complex, multi-oscillator system as it is in birds and lizards and 2) may play a role in maintaining polymorphism in timing of reproductive behavior.     

Chronic dopamine D1, dopamine D2 and combined dopamine D1 and D2 antagonist treatment in Cebus apella monkeys: antiamphetamine effects and extrapyramidal side effects

STUDY DESIGN: This study involved weekly radiographic examination of pinealectomized rats, hamsters, and chickens to observe the development of scoliosis. OBJECTIVES: To determine whether pinealectomy produces scoliosis in animals more closely related phylogenetically to humans than to chickens, namely rats and hamsters, which are representative of mammals. SUMMARY OF BACKGROUND DATA: Pinealectomy in 3-day-old chickens has consistently resulted in the development of scoliosis with many characteristics similar to those seen in patients with adolescent idiopathic scoliosis. It has not been determined whether this phenomenon is restricted solely to chickens or is applicable to other animals, especially those more closely related to humans. METHODS: The pineal gland was removed from young rats, hamsters, and chickens. All animals underwent radiography weekly to detect the development of any scoliosis. Weight and length measurements were also taken weekly, and serum melatonin levels were determined at the time the animals were killed. RESULTS: Scoliosis was not observed in either the rats or the hamsters. In contrast, scoliosis developed in 10 of 21 chickens. Serum melatonin levels in all pinealectomized animals were zero. CONCLUSIONS: In contrast to the chickens, pinealectomy does not seem to cause scoliosis in either young rats or hamsters. The reasons for this discrepancy may include differences in the physiology and spinal morphology of the rat and hamster in comparison with the chicken. In the pinealectomized chickens, the results also suggest that future scoliosis development might be indicated by a significant increase in size when they are compared with pinealectomized chickens that do not develop scoliosis. Such differences in growth rates also distinguish patients with adolescent idiopathic scoliosis.     

Temperature activation of courtship behavior in the male red-sided garter snake (Thamnophis sirtalis parietalis): Role of the anterior hypothalamus-preoptic area.

Adult male red-sided garter snakes (Thamnophis sirtalis parietalis) received radio-frequency lesions prior to 17 weeks of low-temperature hibernation. Animals found to have bilateral lesions of the anterior hypothalamus-preoptic area ({ah-poa}) failed to exhibit courtship behavior on emergence from hibernation. Those individuals in which the major portion of the destruction was centered in the anterior POA also exhibited deficits in thermoregulatory behavior. Animals that received unilateral lesions of the {ah-poa} initiated courtship behavior after controls and had an abbreviated period of courtship; these animals exhibited normal responses to thermal stimuli. Male snakes with lesions outside the {ah-poa} courted normally and demonstrated no differences in thermoregulatory behavior compared with the surgical controls. These results indicate that in male red-sided garter snakes, an intact {ah-poa} is critical for the integration of thermal stimuli that activate seasonal courtship behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate on oxytocin and vasopressin levels in pinealectomized rats during light-dark cycle

Although previous reports have shown that methylphenidate (MPH), in addition to its known behavioral effect, can influence the hypothalamo-pituitary-adrenal axis by increasing the plasma ACTH, the pineal gland seems to be involved in neuroendocrinological processes too, e.g., in hypothalamic synthesis and release of oxytocin (OXY) and vasopressin (AVP). Therefore, a study was performed to measure the OXY and AVP content of the hypothalamus, neurohypophysis, and plasma after application of MPH in the morning and evening in pinealectomized (PE) as well as sham-operated control (SO) rats. Pinealectomy influenced both the daily pattern (reversed in the neurohypophysis) and the levels of OXY and AVP. Starting from this different situation, application of MPH produced diverse effects. Hypothalamus: PE, increase in both hormones in the morning and evening; SO, decrease in morning OXY level. Neurohypophysis: PE, increase in morning OXY level; SO, decrease in both hormones even though in the morning only. Plasma: PE, decrease in morning OXY concentration; SO, increase in both hormones in the morning and decrease in the evening. The present results indicate that MPH application influences the hypothalamo-neurohypophysial system. Furthermore, the hypothesis has been supported that this influence may be dependent on the circadian activity of the pineal gland as well.     

The effects of pineal indoles given late in the light period on reproductive organs and pituitary prolactin levels in male golden hamsters

Intact and pinealectomized adult male hamsters kept in light:dark cycles of 14:10 (in hours) were given daily injections of either 25 microgram melatonin, 5-methoxytryptophol, N-acetylserotonin, or 6-hydroxymelatonin at 19.00 hours (13h after lights on). The injections were continued for 50 consecutive days. The daily melatonin injections significantly elevated body weights and depressed the growth of the testes and accessory sex organs and pituitary prolactin levels in intact hamsters. By comparison, in pinealectomized animals daily afternoon melatonin injections failed to alter body or testicular weights or pituitary prolactin levels. These findings indicate that for single injections of melatonin to be antigonadotrophic in the male hamster, the pineal must be intact. In intact animals, 5-methoxytryptophol and N-acetylserotonin slightly depressed the growth of the reproductive organs and pituitary prolactin levels, respectively. Again, these effects were negated by removal of the pineal gland. 6-Hydroxymelatonin was without influence on any of the parameters of reproduction that were measured.     

Differential effects of mate competition and mate choice on eastern tiger salamanders

Male tiger salamanders, Ambystoma tigrinum tigrinumare slightly larger in body size and have considerably higher and longer tails than females. To determine how these dimorphic traits affected reproductive performance and success, we conducted breeding trials using 12 males and six females per trial and monitored male-female and male-male interactions. Larger males had an advantage in most aspects of mate competition investigated. Males with higher tails had no advantage in either mate competition or mate choice. Males with longer tails also had no advantage in mate competition but were preferred as mates by females. Larger males interrupted courting males more often than smaller males did. The form of male-male interference was conditional on body size and not on either tail dimension. If the intruder was larger than the courting male, it would shove the female away from the courting male and initiate courtship; if the intruder was smaller, it adopted a female mimicry tactic in which it positioned itself between the courting male and female and performed female behaviours to the courting male while simultaneously courting the female. Our trials indicated that the two components of sexual selection may influence the evolution of different male morphological traits in tiger salamanders. Mate competition may favour increased male body length; mate choice may select for greater male tail length.     

Circadian rhythm of biosynthetic activity of the epiphysis in relatively wild and domesticated silver foxes

Circadian dynamics of biosynthetic activity in pineal glands of adult relatively wild and domesticated silver fox females was studied beyond the reproductive season using radioimmune and fluorometric methods. The level of melatonin, the principal pineal hormone; activities of enzymes controlling its biosynthesis; the level of its precursor and one of its metabolites, as well as those of neurotransmitters involved in the regulation of biosynthesis exhibited more or less pronounced circadian changes. The concentration of melatonin in the pineal gland at night was considerably higher in domesticated foxes than in relatively wild ones. The most likely reason for the elevated concentration of melatonin at night is its slow secretion from the pineal glands of domesticated foxes, because its concentration in plasma does not differ from that in relatively wild animals. The results obtained suggest that selection for domestic behavior has affected the adrenergic mechanism of regulation of pineal gland rhythms, as well as other functions of sympathetic divisions of the central nervous system.     

Localization of melatonin in the digestive tract of the rat. Effect of maturation, diurnal variation, melatonin treatment and pinealectomy

Using highly specific antibodies, melatonin was identified in the gastrointestinal tract of the rat as early as several hours of postnatal life. Its amount progressively increased and reached the adult levels around day 21. Exogenously administered melatonin concentrates in all parts of the gastrointestinal tract with most pronounced accumulation in the colon and the rectum. Diurnal variations were not clearly demonstrated in any part of the alimentary canal. Pinealectomy had no visible effect on the levels of melatonin in the tissues investigated. A hypothesis of ontogenic as well as phylogenic development of production of N-acetylated indolealkylamines in the pineal and the extrapineal tissues and their physiological role is presented.     

Theoretical considerations on the nature of the pineal 'ageing clock'

The models developed in our laboratory demonstrate that ageing initiates and progresses in the pineal gland. However, the ageing postponing effects of pineal grafting into older recipients cannot be explained by a simple maintenance and/or normalization of the night melatonin synthesis and release. We propose here that the pineal gland monitors and regulates, via its control of neuroendocrine function, the maintenance of 'self-identity' and the capacity of the immune system to recognize and react against any noxious, endogenous or exogenous agent. Senescence is characterized by the extinction of this central pineal function. The progressive decline of the self-recognition capacity distinguishes the typical diseases of ageing expressed as emergence of peripheral desynchronization and autoimmune, anaplastic, neoplastic and degenerative processes. Our approaches aim at a prevention and/or restoration of central pineal functions.     

Social dynamics of group courtship behavior in male red-sided garter snakes (Thamnophis sirtalis parietalis).

Examined the social dynamics of the formation of mating balls (gatherings of males) during the mating period of red-sided garter snakes to determine whether the mating balls are formed simply because of a common attraction to the female or whether males are stimulated by the mating balls themselves. Nine test males and 9 stimulus females were used in tests, along with 55 other males, to measure the effect of other courting males. Results show that male Ss courted females more actively when other males were also courting the female than when they were alone with her, suggesting that the female is more attractive to the male when courted by other males. A positive correlation was observed between the number of additional males present and the amount of courtship activity shown by the test male toward the stimulus female. The extent to which the courtship activity of the test males was stimulated by the presence of additional courting males was not influenced by how actively the additional males courted. Results suggest that males are intrinsically stimulated by mating balls. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The butyrylcholinesterase gene is neither independently nor synergistically associated with late-onset AD in clinic- and community-based populations

Pituitary adenylate cyclase-activating polypeptide (PACAP) was recently demonstrated to stimulate melatonin synthesis in the rat pineal gland. Circadian rhythms of melatonin concentration are well known. However, it has not been clarified whether PACAP contents in the pineal gland show circadian rhythm. In this study, we measured PACAP contents in the rat pineal gland throughout the day under 12:12 h light-dark cycle or constant dark conditions. A significant fluctuation was observed in the PACAP content under light-dark conditions but not under constant darkness. On the other hand, the pituitary gland showed no significant variation throughout the day under either conditions. These observations suggest that PACAP may participate in the modulation of melatonin synthesis depending on light conditions in the pineal gland.     

The pineal affects life span in hamsters with heart disease

Cardiomyopathic hamsters (CMH) develop heart disease early in life which leads to congestive heart failure and death as these hamsters age. We have previously shown that living in constant light or other non-24-h light-dark (LD) cycles can increase longevity in these hamsters, and the current experiment examined potential mechanisms for this effect. Thus, CMH were orchidectomized, pinealectomized, or given melatonin treatment and then placed on either 1:23 or 1:23.6 LD cycles. Orchidectomy had no effect on longevity in either LD cycle, but in 1:23.6 it did lead to death with a greater degree of heart failure. On the other hand, pinealectomy of 1:23 CMH led to changes in life span similar to those produced by placing the hamsters in 1:23.6. Moreover, melatonin implant treatment of CMH in 1:23.6 led to changes in life span that were similar to those caused by life in 1:23, at least over the first half of the survival curves. Thus, it appears that the pineal gland and melatonin may be involved in mediating the effects of non-24-h LD cycles, whether these effects are beneficial or detrimental. In addition, the testes and testosterone appear to have no role in mediating these effects. These data suggest that inhibition, rather than stimulation, of pineal function might be beneficial for those with congestive heart failure, but further experiments are necessary to clarify when during the disease process potential treatments might be helpful.     

Sigma receptor modulation of noradrenergic-stimulated pineal melatonin biosynthesis in rats

Because sigma receptors are richly concentrated in the rat pineal gland, the present study was performed to investigate their possible role in the modulation of melatonin production. To this purpose, we assessed in vivo the effects of the sigma-receptor ligands 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine on the rat pineal gland activity during either the daytime or the nighttime. Compared with vehicle, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine potentiated the enhancement of N-acetyltransferase activity and pineal melatonin content induced by isoproterenol administration during the daytime, whereas they did not affect the diurnal basal biosynthetic activity of the gland. Conversely, at night, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine enhanced significantly the physiological increases in both pineal N-acetyltransferase activity and melatonin levels. This enhancement was prevented by pretreatment with rimcazole, a specific sigma-receptor antagonist. These findings suggest that, in rats, the activation of pineal sigma-receptor sites does not affect the biosynthetic activity of the pineal gland during daytime, whereas it potentiates the production of melatonin when the gland is noradrenergically stimulated either by isoproterenol administration or by the endogenously released norepinephrine at nighttime.     

Differences in the UV-crosslinking patterns of the poliovirus 5''-untranslated region with cell proteins from poliovirus-susceptible and -resistant tissues

Specific polyclonal antibody was raised against D-aspartate (D-Asp) which had been conjugated to glutaraldehyde and was purified by affinity chromatography. Immunohistochemical staining of rat pineal gland with the antibody demonstrated the presence of D-Asp in the cytoplasm of pinealocytes, the predominant cell type in this gland. D-Asp immunoreactivity was more evident in the distal region than in the proximal region of the gland. Pinealocytes in the distal region are presumably involved in the synthesis and secretion of the pineal hormone, melatonin, and the results of staining may indicate some yet unknown role of D-Asp in the regulation of melatonin secretion.     

Effects of pinealectomy of rams on secretory profiles of luteinizing hormone, testosterone, prolactin and cortisol

In a study of pineal gland influences on hormone secretory profiles, blood samples were collected at 20 min intervals for 26 h from 4 pinealectomized and 4 sham-operated rams which were subjected to a 14.5 h daily photoperiod. Plasma levels of luteinizing hormone (LH) and testosterone (T) underwent rapid pulsatile fluctuations in all rams. Pinealectomized rams produced more LH than the sham-operated rams and a similar trend was recorded for plasma T data, since T secretion closely followed that of LH. A nocturnal elevation of plasma prolactin (Prl) levels displayed by sham-operated rams was substantially abolished by pinealectomy. Also a rise in cortisol secretion during the morning hours recorded from 3 of the sham-operated rams was absent in 2 of the pinealectomized rams. The possible significance of the pineal gland in the regulation of secretion of these hormones is discussed.     

The antisteroid action on the pineal gland

The study presents the data gathered along the years on the antisteroid action of the pineal gland. Thus, it was demonstrated that administration of pineal polypeptides to the rabbit lowers the urinary 17-KS both of testicular and adrenal origin. Conversely, pinealectomy caused an increase in the level of these steroid hormones. The same pineal material induced a marked decrease both in the serum and testicular testosterone and in the plasma and adrenal corticosterone in the rat. At the same time administration of pineal polypeptides lowered the cholesterol in the serum, bile, liver, testis and adrenal. Melatonin had no effect on these biochemical indices, which demonstrates that the effects obtained with pineal polypeptides are not mediated by melatonin.     

Effects of intracellular free cholesterol accumulation on macrophage viability: a model for foam cell death

A prominent innervation of the pineal gland of the European hamster with nerve fibres containing neuropeptide Y (NPY) and tyrosine hydroxylase (TH) was demonstrated by means of immunohistochemistry. Nearly all the TH- and NPY-immunoreactive nerve fibres in the superficial pineal gland disappeared after bilateral superior cervical ganglionectomy, showing that the majority of NPY- and TH-immunoreactive nerve fibres belonged to the sympathetic nervous system. Since, in the European hamster, preliminary studies of the NPY-fibre density in the pineal gland had indicated seasonal changes, the density of NPY-immunoreactive nerve fibre profiles was ascertained in the superficial pineal gland in a series of animals between the first part of November and late April. The highest density of NPY-immunoreactive nerve fibre profiles was observed during midwinter. On the other hand, during the same period of the year, the number of sympathetic TH-immunoreactive sympathetic nerve fibre profiles did not exhibit seasonal variation, nor did substitution of testosterone, during the sexually inactive period, affect the density of NPY-containing nerve fibres in the gland. Our results show the presence of a testosterone-independent annual variation in the content of NPY in the sympathetic nerve fibres innervating the pineal gland of the European hamster. This variation can be correlated with the changes in the daily pattern of melatonin production observed by others in the same species at this period of the year.     

Temporal manipulation of ejaculate components by newly fertilized Drosophila melanogaster females

Observations of newly mated Drosophila melanogaster females suggest that females control the times at which components of the ejaculate cause behavioural and physiological changes characteristic of fertilized females. Females that were assayed immediately after they mated elicited as much courtship as they did when they were virgins, but were unreceptive to copulation. Within a few minutes of when they disengaged from copulation, most females performed ovipositor extrusion, which has been classified as a rejection behaviour, in response to courting males or males that had previously performed courtship. Most females that were assayed immediately after mating had already ovulated. The females, however, do not begin to lay eggs until 4-6 h after mating, at which time they elicit very little courtship (Scott & Richmond 1985, Anim. Behav., 33, 817-824). Our observations suggest that neither ovipositor extrusion nor male-synthesized pheromones that are transferred to females' cuticles during copulation inhibit males' courtship of newly fertilized females. Thus, males cannot determine that newly fertilized females are unreceptive to copulation. These observations also indicate that the failure of newly fertilized females to mate with males is not a consequence of the females' inability to elicit vigorous courtship. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

The conjoint relationships of the epiphysis and hippocampus in the shaping of the reaction to stress

Pinealectomy and electrolytic destruction in different directions changed the behaviour of rats in a conflict situation and the temporal organization of forced swimming. Combination of both kinds of surgery decreased the behavioural shifts produced by the hippocampal lesions. It is suggested that the anti-stressor properties of the pineal gland can be realized through changes in the hippocampal function state.     

Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields

The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 microT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 microT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of <5 microW/cm2). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation.