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A Kalsbeek

Publications and source records attributed to A Kalsbeek.

At least 37 records · Page 2Linked to original sources
PubMed2000

Polysynaptic neural pathways between the hypothalamus, including the suprachiasmatic nucleus, and the liver.

The suprachiasmatic nucleus of the hypothalamus is responsible for a 24-h rhythm in basal glucose levels in the rat. The neural pathways used by the suprachiasmatic nucleus to mediate this rhythm in plasma glucose have not yet been identified. In the present study we examined whether there are any connections between hypothalamic centers, including the suprachiasmatic nucleus, and the liver, which is the main site for glucose production and storage. Transneuronal virus tracing from the liver showed that after injection of pseudorabies virus, specific neuronal cell populations in the central nervous system were labeled retrogradely, suggesting that specific sites in the central nervous system may control liver metabolism. First-order neurons belonged to the sympathetic and parasympathetic system, while second-order and third-order neurons were present in both the brainstem and hypothalamus. The presence of third-order neurons in the suprachiasmatic nucleus suggests an involvement of the biological clock in the neural control of the liver.

Animals↗
PubMed2000

Potentiation effect of vasopressin on melatonin secretion as determined by trans-pineal microdialysis in the Rat.

The mammalian pineal gland is known to receive a noradrenergic innervation originating from the superior cervical ganglion which corresponds to the primary regulatory input for melatonin synthesis. However, many peptidergic fibers containing peptides such as vasopressin and oxytocin have also been found in the rat pineal gland. The present study was performed to investigate the possible role of vasopressin and oxytocin on melatonin secretion in vivo. Therefore, both neuropeptides were delivered for 2 h through a trans-pineal microdialysis probe directly into the gland at different times during the nocturnal phase of the light:dark cycle. At the same time pineal dialysates were collected continuously. Melatonin concentrations were measured by radioimmunoassay. Melatonin synthesis potentiation was achieved when vasopressin was infused locally in the pineal, during the onset of nocturnal melatonin secretion. In order to assess the possible role of a physiological increase of endogenous circulating vasopressin on pineal metabolism, melatonin synthesis was recorded in the same animals before and after a prolonged dehydration period. Night time melatonin concentration was increased after the water deprivation vs control conditions. Contrary to that, oxytocin seems not to affect pineal metabolism in the rat since no significant change was observed on melatonin secretion in response to a local oxytocin infusion. These results show that vasopressin can modulate melatonin synthesis in the rat pineal whereas no effect was obtained with oxytocin, at least under the present experimental conditions.

Animals↗
PubMed2000

Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin.

Despite a pronounced inhibitory effect of light on pineal melatonin synthesis, usually the daily melatonin rhythm is not a passive response to the surrounding world. In mammals, and almost every other vertebrate species studied so far, the melatonin rhythm is coupled to an endogenous pacemaker, i.e. a circadian clock. In mammals the principal circadian pacemaker is located in the suprachiasmatic nuclei (SCN), a bilateral cluster of neurons in the anterior hypothalamus. In the present paper we show in the rat that bilateral abolition of gamma-aminobutyric acid (GABA), but not vasopressin, neurotransmission in an SCN target area, i.e. the paraventricular nucleus of the hypothalamus, during (subjective) daytime results in increased pineal melatonin levels. The fact that complete removal of the SCN results in a pronounced increase of daytime pineal mRNA levels for arylalkylamine N-acetyltransferase (AA-NAT), i.e. the rate-limiting enzyme of melatonin synthesis, further substantiates the existence of a major inhibitory SCN output controlling the circadian melatonin rhythm.

Animals↗
PubMed2000

Restricted daytime feeding attenuates reentrainment of the circadian melatonin rhythm after an 8-h phase advance of the light-dark cycle.

It is well established that in the absence of photic cues, the circadian rhythms of rodents can be readily phase-shifted and entrained by various nonphotic stimuli that induce increased levels of locomotor activity (i.e., benzodiazepines, a new running wheel, and limited food access). In the presence of an entraining light-dark (LD) cycle, however, the entraining effects of nonphotic stimuli on (parts of) the circadian oscillator are far less clear. Yet, an interesting finding is that appropriately timed exercise after a phase shift can accelerate the entrainment of circadian rhythms to the new LD cycle in both rodents and humans. The present study investigated whether restricted daytime feeding (RF) (1) induces a phase shift of the melatonin rhythm under entrained LD conditions and (2) accelerates resynchronization of circadian rhythms after an 8-h phase advance. Animals were adapted to RF with 2-h food access at the projected time of the new dark onset. Before and at several time points after the 8-h phase advance, nocturnal melatonin profiles were measured in RF animals and animals on ad libitum feeding (AL). In LD-entrained conditions, RF did not cause any significant changes in the nocturnal melatonin profile as compared to AL. Unexpectedly, after the 8-h phase advance, RF animals resynchronized more slowly to the new LD cycle than AL animals. These results indicate that prior entrainment to a nonphotic stimulus such as RF may "phase lock" the circadian oscillator and in that way hinder resynchronization after a phase shift.

Animals↗
PubMed2000

Functional connections between the suprachiasmatic nucleus and the thyroid gland as revealed by lesioning and viral tracing techniques in the rat.

Frequent blood sampling via intraatrial cannula revealed daily rhythms of TSH and thyroid hormones in both male and female Wistar rats. Thermic ablation of the biological clock, i.e. the suprachiasmatic nucleus (SCN), eliminated the diurnal peak in circulating TSH and thyroid hormones. In addition, SCN lesions produced a clear decrease of 24-h mean T4 concentrations. A more pronounced effect of SCN-lesions on thyroid hormones, as opposed to TSH, suggested routes of SCN control additional to the neuroendocrine hypothalamopituitary-thyroid axis. Retrograde, transneuronal virus tracing was used to identify the type and localization of neurons in the central nervous system that control the autonomic innervation of the thyroid gland. In the spinal cord and brain stem, both the sympathetic and parasympathetic motorneurons were labeled. By varying the postinoculation survival time, it was possible to follow the viral infection as it proceeded. Subsequently, the pseudorabies virus (PRV) infected neurons in several brain stem cell groups, the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (second order labeling). Among PRV-infected neurons in the PVN were TRH-containing cells. Third order neurons were found in several hypothalamic cell groups, among which was the SCN. Therefore, we propose that the SCN has a dual control mechanism for thyroid activity by affecting neuroendocrine control of TSH release on the one hand and the autonomic input to the thyroid gland on the other.

Amygdala↗
PubMed1999

GABA release from suprachiasmatic nucleus terminals is necessary for the light-induced inhibition of nocturnal melatonin release in the rat.

The daily rhythm of melatonin production in the mammalian pineal is driven by the endogenous circadian pacemaker in the suprachiasmatic nuclei. The major release period of melatonin is closely linked to the dark phase of the 24-h day/night cycle. Environmental light will affect melatonin release in two ways: (i) it entrains the rhythm of the circadian oscillator; and (ii) it causes an acute suppression of nocturnal melatonin release. These two effects of light are both mediated by the suprachiasmatic nucleus and enable the pineal gland to convey information about day length to the reproductive system through changes in melatonin levels. Glutamate is currently believed to be the major transmitter in the retinal ganglion cell fibers reaching the suprachiasmatic nucleus. At present no information is available, however, about the transmitter(s) implicated in the further propagation, i.e. from the suprachiasmatic nucleus onwards, of the light information. In the present study we provide evidence that the endogenous release of GABA from suprachiasmatic nucleus terminals is implicated in the further transmission of light information to the pineal gland. Bilateral administration of the GABA-antagonist bicuculline to hypothalamic target areas of the suprachiasmatic nucleus completely prevents the inhibitory effect of nocturnal light on melatonin secretion and the present study thus documents that retina-mediated photic activation of suprachiasmatic nucleus neurons induces the release of GABA from efferent suprachiasmatic nucleus nerve terminals, resulting in an inhibition of melatonin release by the pineal gland. Together with our previous (electro)physiological data these results identify GABA as an important mediator of rapid synaptic transmission of suprachiasmatic nucleus output to its target areas.

Animals↗
PubMed1999

Vasopressin induces a luteinizing hormone surge in ovariectomized, estradiol-treated rats with lesions of the suprachiasmatic nucleus.

The luteinizing hormone surge in the female rat is the result of the integration of multiple signals within the medial preoptic area. The medial preoptic area contains gonadotropin-releasing hormone neurons that are responsible for the release of luteinizing hormone, neurons containing estrogen receptors and terminals originating from the suprachiasmatic nucleus with, for example, vasopressin as neurotransmitter. Both the medial preoptic area and suprachiasmatic nucleus are crucial for the occurrence of luteinizing hormone surges, since lesioning of either nucleus prevents pre-ovulatory and steroid-induced luteinizing hormone surges. In this study, we investigated whether vasopressin in the medial preoptic area could be the daily neuronal signal from the suprachiasmatic nucleus responsible for the timing of the luteinizing hormone surge. Vasopressin (50 ng/microl) or Ringer solution was administered by reverse microdialysis from Zeitgeber times 7.5 to 12.5 into the medial preoptic area of ovariectomized, estradiol-treated rats. The suprachiasmatic nucleus was lesioned to remove all cyclic luteinizing hormone secretion. This was evaluated by monitoring behavioral activity; animals that were arrhythmic were included in the experiments. Hourly blood samples were taken to measure plasma luteinizing hormone levels. Preoptic vasopressin administration induced a surge-like luteinizing hormone pattern in suprachiasmatic nucleus-lesioned animals, whereas constant, basal luteinizing hormone levels were found in the control animals. These data show that vasopressin, by itself, is able to trigger the luteinizing hormone surge in suprachiasmatic nucleus-lesioned rats. We propose that vasopressin is a timing signal from the suprachiasmatic nucleus responsible for the activation of the hypothalamo-pituitary-gonadal axis in the female rat.

Animals↗
PubMed1999

A suprachiasmatic nucleus generated rhythm in basal glucose concentrations.

The daily rhythm in feeding activity in mammals, as driven by the biological clock, largely determines the daily fluctuations in basal concentrations of glucose and insulin. To investigate a possible direct impact of the suprachiasmatic nucleus (SCN) on these parameters, we subjected intact rats and SCN-lesioned rats to a fasting regimen of 36 h, or to a scheduled feeding regimen of six identical meals equally distributed over the light:dark-cycle. Plasma profiles of glucose and insulin in rats during the final 24 h of the 36 h of fasting, and in rats subjected to the scheduled feeding regimen were compared to profiles in rats fed ad libitum. In rats fed ad libitum, in fasted rats and in rats subjected to a scheduled feeding regimen basal glucose concentrations showed a pronounced 24-h rhythm that was not found in rats that had been SCN-lesioned. Basal insulin levels showed a 24-h rhythm in 50% of the rats fed ad libitum and in 50% of the rats subjected to a scheduled feeding regimen; neither rhythms were present in SCN-lesioned rats. However, none of the fasted rats showed a 24-h rhythm in basal insulin concentrations. These data provide clear evidence that the SCN directly controls basal glucose concentrations independent of its influence on feeding activity. At the same time, we found no consistent evidence for a strong impact of the SCN on basal insulin concentrations.

Animals↗
PubMed1999

Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway.

In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.

Adrenal Cortex↗
PubMed1999

Interindividual differences in the pattern of melatonin secretion of the Wistar rat.

In vivo trans-pineal microdialysis was performed in male Wistar rats maintained under a 12 hr light:12 hr dark (LD 12:12) cycle. Collected dialysates were assayed by radioimmunoassay for melatonin concentrations. A non-linear regression was fitted through the obtained datapoints to determine the time points at which a 50% increase (IT50) and decrease (DT50) of the nocturnal melatonin peak were reached. In a first experiment, the nocturnal melatonin profiles of four animals were determined throughout 5 consecutive days. In a second experiment, we analysed the melatonin profiles during the night in rats originating from three different breeding colonies (Dépré Harlan, and Iffa-Cŕedo). A low intraindividual variability was found on the phase markers IT50 and DT50, as on peak duration of melatonin rhythms estimated over 5 subsequent days in the same animal. In contrast, animals showed a large interindividual variability in their profile phase markers and the values were dependent on the origin of the breeding colony. Each rat colony was characterized by early or late IT50 and DT50 as long or short peak length. It is concluded from experiment 1 that the melatonin rhythm is a very stable circadian marker. Nevertheless, great caution must be taken in the choice of animal groups while studying circadian rhythms due to the large interindividual variability observed in experiment 2. Therefore, as the technique allows the use of the animal as its own control, the present study demonstrated that the use of the microdialysis technique is of interest in studies on the circadian system.

Animals↗
PubMed1998

Circadian control of insulin secretion is independent of the temporal distribution of feeding.

To investigate whether there is a circadian regulation of insulin secretion, rats were adapted to a feeding regimen of six meals equally distributed over 24 h. Under these conditions basal glucose and insulin levels increased during the light phase and decreased during the dark phase. Maximal blood glucose responses were fairly similar during the six different meals, but glucose increments were clearly delayed during the last two meals consumed during the light period. Insulin increments were highest during the dark phase and clearly diminished during the second half of the light phase. This situation was reversed when the scheduled meals were replaced by i.v. glucose infusions, i.e., no significant differences were detected between insulin responses, whereas glucose increments were reduced during the dark period. These results show that there is a circadian regulation of basal blood glucose and feeding-induced insulin responses, which is independent of the temporal distribution of feeding activity.

Animals↗
PubMed1998

The suprachiasmatic nucleus-paraventricular nucleus interactions: a bridge to the neuroendocrine and autonomic nervous system.

Vasopressin (VP) is one of the principal neurotransmitters of the suprachiasmatic nucleus (SCN). By means of anatomical, physiological and electrophysiological techniques we have demonstrated that VP containing pathways from the SCN serve to affect neuroendocrine and 'autonomic' neurons in the paraventricular nucleus. By direct and indirect connections VP serves to inhibit corticosterone secretion, not only by affecting ACTH secretion but also by controlling the adrenal cortex via a neuronal route. Apart from controlling the pineal and adrenal, we also observed that the SCN is able to influence the heart. Subjecting rats or humans to light affects heart rate in a dose-dependent manner. These results suggest an important role for the SCN and VP in the SCN in the regulation of neuroendocrine and autonomic functions.

Animals↗
PubMed1998

Restricted daytime feeding modifies suprachiasmatic nucleus vasopressin release in rats.

The authors have shown previously that vasopressin (VP) release from suprachiasmatic nucleus (SCN) efferents in rats is important for the timing of the circadian activity of the hypothalamo-pituitary-adrenal (HPA) axis, resulting in a circadian rise in corticosterone at dusk. When meals are supplied at a fixed time during the light period, however, this normal circadian activity of the HPA axis is strongly modified. Under such a restricted feeding regimen, a corticosterone peak appears just before the daily meal in addition to the circadian corticosterone peak at dusk. This feeding-associated rise in corticosterone is regarded as an SCN-independent circadian rhythm because it is sustained in SCN-lesioned animals. Despite these previous results, the authors investigated a putative involvement of SCN-derived VP in the control of the prefeeding corticosterone peak by measuring the intranuclear release of VP in the SCN and plasma corticosterone levels in rats in ad libitum feeding conditions as well as in animals that were obliged to feed during a 2-h period in the middle of the light period. Restricted daytime feeding caused clear changes in the daily release pattern of VP from SCN terminals. Both a delayed onset of the diurnal rise and a premature decline of the elevated daytime levels were observed, but the acrophase of the VP rhythm was not phase shifted. Concerning the circadian corticosterone peak, no phase shift of its acrophase was observed either. It is concluded that (1) restricted daytime feeding does affect SCN activity, (2) intranuclear release of VP within the SCN is an important mechanism to amplify and synchronize the circadian rhythms as dictated by the light/dark-entrained circadian pacemaker, and (3) VP release observed in animals on restricted feeding is completely compatible with the previously proposed inhibitory action of SCN-derived VP on the HPA axis.

Animals↗
PubMed1997

Novel environment induced inhibition of corticosterone secretion: physiological evidence for a suprachiasmatic nucleus mediated neuronal hypothalamo-adrenal cortex pathway.

Basal plasma ACTH and corticosterone levels are controlled by the suprachiasmatic nucleus (SCN), the site of the circadian pacemaker, resulting in a daily peak in plasma corticosterone and ACTH. The present study was carried out to investigate the mechanisms employed by the biological clock to control these hormones. Novel environment induced changes in plasma ACTH and corticosterone in intact and SCN-lesioned animals were employed as experimental approach. Placing intact animals in a new environment results in different plasma corticosterone and ACTH responses depending on the clock time of the stimulus. (1) Novel environment (2 h after onset of darkness (ZT14)) results in a fast decrease followed by an increase in corticosterone. This changing pattern in corticosterone secretion was not accompanied by any change in plasma ACTH, suggesting a direct neuronal control of the adrenal cortex. (2) In contrast, novel environment at 2 h after light onset (ZT2) results in a rapid increase in plasma ACTH. Regression analysis of the relation ACTH-corticosterone before and after stress shows a changed pattern at ZT2, although at that time still no significant correlation between ACTH and corticosterone was detected. AT ZT14 this correlation was only present after stress. (3) SCN lesioning results in low basal ACTH at all circadian times combined with elevated corticosterone levels. Here, a new environment results in an immediate increase in corticosterone without inhibition; ACTH also increases rapidly, but attains lower levels than at ZT2 in intact animals. (4) The present results therefore demonstrate SCN modulating corticosterone secretion by affecting ACTH secretion and changing the sensitivity of the adrenal cortex by means of a neuronal input.

Adrenal Cortex↗
PubMed1997

Direct vasoactive intestinal polypeptide-containing projection from the suprachiasmatic nucleus to spinal projecting hypothalamic paraventricular neurons.

In mammals, photoperiodic information is conveyed from the retina to the pineal through a polysynaptic pathway, which includes the suprachiasmatic nucleus (SCN), the paraventricular nucleus of the hypothalamus (PVN), the spinal preganglionic neurons and, finally, the superior cervical ganglion. Precise data on the site in the PVN or which SCN transmitters are involved in the transmission of information in this pathway is lacking. In the present experiment we investigated whether SCN efferents containing vasoactive intestinal polypeptide (VIP) innervate PVN neurons that project to the spinal cord. A combination of retrograde tracing and immunocytochemistry with the aid of a confocal laser scanning microscope allowed us to assess possible interaction of SCN efferents and spinal cord projecting neurons in the PVN. Approximately 30% of identified autonomic projecting neurons in the dorsal PVN and 40% in the ventral PVN received VIP innervation mainly on their dendrites. These results provide further evidence for the involvement of SCN-derived VIP in the transmission of circadian information to the pineal.

Animals↗
PubMed1997

Oxytocin innervation of spinal preganglionic neurons projecting to the superior cervical ganglion in the rat.

The paraventricular nucleus of the hypothalamus is a major integrative nucleus for relaying information from the suprachiasmatic nucleus to the autonomic system. The precise pathway by which this information can influence autonomic functions, such as melatonin synthesis in the pineal gland, is not clear. In the present study, we used a retrograde tracer injected in the superior cervical ganglion to identify spinal preganglionic neurons. One of the main neurotransmitters present in descending projections of the paraventricular nucleus of the hypothalamus, oxytocin, was detected with immunocytochemistry to visualise possible contacts with the neurons located in the intermediolateral column of the spinal cord and projecting to the superior cervical ganglion. Although many appositions could be seen at the light-microscopic level, this abundance could not be confirmed at the electron-microscopic level. The implications of these observations for the overall timing message received by the spinal preganglionic neurons are discussed.

Animals↗
PubMed1996

A diurnal rhythm of stimulatory input to the hypothalamo-pituitary-adrenal system as revealed by timed intrahypothalamic administration of the vasopressin V1 antagonist.

The mammalian suprachiasmatic nuclei (SCN) contain an endogenous pacemaker that generates daily rhythms in behavior and secretion of hormones. We hypothesized that the SCN imposes its circadian rhythm on the rest of the brain via a rhythmic release of its transmitters in its target areas. Previously, we demonstrated a pronounced inhibitory effect of vasopressin (VP), released from SCN terminals in the dorsomedial hypothalamus, on the release of the adrenal hormone corticosterone. In the present study, microdialysis-mediated intracerebral administration of the VP V1-receptor antagonist was used to pursue the study of the mechanisms underlying the circadian control of basal corticosterone release. Using timed administrations of the VP antagonist divided equally over the day/night cycle, we were able to uncover the existence of an additional stimulatory input from the SCN to the hypothalamopituitary-adrenal (HPA) axis. Peak activity of this stimulatory SCN input takes place during the second half of the light period, after the daily peak of VP secretion, with a delay of approximately 4-6 hr. In all likelihood, the inhibitory and stimulatory circadian input via separate mechanisms affects corticosterone release. Together, these two opposing circadian control mechanisms of the HPA axis enable a precise timing of the circadian peak in corticosterone release.

Adrenocorticotropic Hormone↗