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At least 829 records · Page 46Linked to original sources
PubMed1997

Evidence from confocal fluorescence microscopy for a dense, reciprocal innervation between AVP-, somatostatin-, VIP/PHI-, GRP-, and VIP/PHI/GRP-immunoreactive neurons in the rat suprachiasmatic nucleus.

The rat suprachiasmatic nucleus (SCN) consists of several classes of neurons which can be identified by their transmitter content. Knowledge of putative interaction between these different cell types is essential in order to understand the possibilities of information processing within the SCN. The aim of the present study was therefore to obtain more information about the mutual innervation between the main cell classes in the rat SCN, viz. those containing the neuropeptides arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), gastrin-releasing peptide (GRP) and somatostatin respectively. For this purpose, vibratome sections were double-immunolabelled for seven different peptide combinations and subsequently analysed by high-resolution confocal laser scanning fluorescence microscopy. Attention was focused on axosomatic appositions, the occurrence and frequency of which were quantitatively estimated. Our analysis of double-immunolabelled sections demonstrated that some of the VIP- and some of the GRP-immunoreactive nerve cells and endings showed colocalization. Assuming, on the basis of literature data, that VIP and PHI are always colocalized at the cellular level, the five main cell classes in the SCN appeared to be interconnected, at least axosomatically, in the following reciprocal way: AVP <--> VIP/PHI, AVP <--> GRP, AVP <--> somatostatin, somatostatin <--> VIP/PHI, somatostatin <--> GRP, VIP/PHI <--> GRP, VIP/PHI/GRP <--> GRP, VIP/PHI/GRP <--> VIP/ PHI. In addition to this heterologous axosomatic innervation, these cell groups also showed substantial homologous innervation. Supported by electron microscope data from the literature showing the existence of axodendritic synapses for some of these peptide combinations, our findings strongly suggest that the rat SCN comprises a complex synaptic network with strong interactive capabilities, which is probably a requisite for its biological clock function.

Animals↗
PubMed2004

Rhythmic regulation of membrane potential and potassium current persists in SCN neurons in the absence of environmental input.

Neurons of the mammalian suprachiasmatic nucleus (SCN) generate self-sustained rhythms of action potential frequency having a period of approximately 24 h. It is generally believed that cell autonomous circadian oscillation of a network of biological clock genes drives the circadian rhythm in neuronal firing rate through as yet unspecified effects on the neuronal membrane. While it is clear that cyclic gene expression continues in constant darkness, previous studies have not examined which specific membrane properties of SCN neurons continue to oscillate in constant conditions. Here, we demonstrate that SCN neurons exhibit robust rhythms in resting membrane potential and input resistance in constant darkness. Furthermore, application of the K+ channel blocker tetraethylammonium revealed a rhythm in K+ current amplitude that persists in constant darkness and underlies the rhythm in membrane potential.

Animals↗
PubMed2005

Tissue-specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles.

Serotonin (5-HT) is involved in both photic and non-photic synchronization of the mammalian biological clock located in the suprachiasmatic nuclei (SCN). We have previously demonstrated that tryptophan hydroxylase protein (TPH), the rate-limiting enzyme of 5-HT synthesis, shows circadian rhythmicity in the pathways projecting from the raphe nuclei to the intergeniculate leaflets of the thalamus on one hand, and to the SCN on the other hand. In this study, we investigate whether the circadian rhythmicity in TPH protein could result from the rhythmic expression of tph gene in the raphe nuclei. We thus cloned specific tph1 and tph2 partial cDNAs and assessed the daily profiles of TPH mRNA levels by in situ hybridization in the rat raphe nuclei. Our results demonstrate that: (i) tph2 gene is exclusively expressed in the raphe nuclei, whereas tph1 gene is expressed in the pineal gland; (ii) under light-dark cycle (LD), TPH2 mRNA levels present daily variation within both median and dorsal raphe nuclei; (iii) under constant darkness TPH2 mRNA levels in both nuclei exhibit the same variation reported under LD cycle. These data show that the circadian 5-HT synthesis within the serotonergic neurons projecting to the circadian system might be explained by the rhythmic transcription of the tph2 gene in raphe nuclei. Taking our result with previous data into consideration, we further suggest that 5-HT synthesis and release within the circadian system could be directly or indirectly under the control of the SCN.

Animals↗
PubMed2006

A sleep study in cluster headache.

Cluster headache (CH) is a primary headache with a close relation to sleep. CH presents a circa-annual rhythmicity; attacks occur preferably during the night, in rapid eye movement (REM) sleep, and they are associated with autonomic and neuroendocrine modifications. The posterior hypothalamus is the key structure for the biological phenomenon of CH. Our aim is to describe a 55-year-old man presenting a typical episodic CH, in whom we performed a prolonged sleep study, consisting of a 9-week actigraphic recording and repeated polysomnography, with evaluation of both sleep macrostructure and microstructure. During the acute bout of the cluster we observed an irregular sleep-wake pattern and abnormalities of REM sleep. After the cluster phase these alterations remitted. We conclude that CH was associated, in this patient, with sleep dysregulation involving the biological clock and the arousal mechanisms, particularly in REM. All these abnormalities are consistent with posterior hypothalamic dysfunction.

Cluster Headache↗
PubMed1998

Synaptic inhibition: its role in suprachiasmatic nucleus neuronal thermosensitivity and temperature compensation in the rat.

1. Whole-cell patch clamp recordings of neurones in the suprachiasmatic nucleus (SCN) from rat brain slices were analysed for changes in spontaneous synaptic activity during changes in temperature. While recent studies have identified temperature-sensitive responses in some SCN neurones, it is not known whether or how thermal information can be communicated through SCN neural networks, particularly since biological clocks such as the SCN are assumed to be temperature compensated. 2. Synaptic activity was predominantly inhibitory and mediated through GABAA receptor activation. Spontaneous inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were usually blocked with perifusion of 10-50 microM bicuculline methiodide (BMI). BMI was used to test hypotheses that inhibitory synapses are capable of either enhancing or suppressing the thermosensitivity of SCN neurones. 3. Temperature had opposite effects on the amplitude of IPSPs and IPSCs. Warming decreased IPSP amplitude but increased IPSC amplitude. This suggests that thermally induced changes in IPSP amplitude are primarily influenced by resistance changes in the postsynaptic membrane. The thermal effect on IPSP amplitude contributed to an enhancement of thermosensitivity in some neurones. 4. In many SCN neurones, temperature affected the frequency of IPSPs and IPSCs. An increase in IPSP frequency with warming and a decrease in frequency during cooling made several SCN neurones temperature insensitive, allowing these neurones to maintain a relatively constant firing rate during changes in temperature. This temperature-adjusted change in synaptic frequency provides a mechanism of temperature compensation in the rat SCN.

Animals↗
PubMed2000

Inhibition of sarcoplasmic reticulum function by polyunsaturated fatty acids in intact, isolated myocytes from rat ventricular muscle.

1. We have studied the effects of two polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on spontaneous and electrically stimulated contractions in single, isolated ventricular myocytes from rat hearts. 2. The frequency of spontaneous waves of calcium release and contraction (induced by elevation of the bathing calcium concentration) is reduced in the presence of EPA. At the same time the resting level of intracellular calcium falls, the resting cell length increases and the amplitude of shortening decreases. All these effects are reversed on removal of EPA. 3. Imaging of the waves of calcium release shows that the amplitude and the rate of propagation of the wave is increased in EPA. Consistent with the increased amplitude, integration of the caffeine-induced Na+-Ca2+ exchange current (a measure of the sarcoplasmic reticulum (SR) calcium content) is increased by both EPA and DHA. 4. EPA has a maintained negative inotropic effect on voltage clamped myocytes. This seems to be entirely due to inhibition of the L-type calcium current. Smaller depolarising pulses in control conditions that elicit the same calcium current as in EPA also activate the same level of contraction. This is in spite of the increased SR calcium content in EPA. 5. It is concluded that PUFAs have two effects on the SR; they reduce the availability of calcium for uptake and they inhibit the release mechanism. Both of these effects should lower the frequency of spontaneous waves of calcium release. As spontaneous release of calcium can initiate arrhythmias, some of the anti-arrhythmic action of PUFAs must be exerted at the level of the SR.

Action Potentials↗
PubMed1980

Regulation of the cycle in chick pineal serotonin N-acetyltransferase activity in vitro by light.

The diurnal cycle in vivo in the level of serotonin N-acetyltransferase (NAT) activity found in the pineal gland of chicks kept under diurnal lighting was reproduced in vitro with glands incubated in organ culture under the same diurnal lighting conditions. We have examined the effects of varying the lighting conditions of culture upon development of NAT activity in vitro with pineal glands from birds which were killed at different times during the photoperiod in vivo. The ability of chick pineal glands to develop increased NAT activity in culture during the dark period of a diurnal cycle of illumination was determined primarily by the proportion of the photoperiod in vivo elapsed at the time of sacrifice of the birds. The time of development of maximal NAT activity in cultured chick pineal glands could be advanced or delayed by corresponding changes in time of start of the dark period. However, the 'settings' of the pineal 'biological clock' remained unchanged. Glands from birds sacrificed in the final 30 min of the photoperiod in vivo developed increased NAT activity without lag when cultured in the light. Similarly, pineal glands cultured under continuous illumination developed an increased photostable NAT activity beginning at the time of the "subjective" end of the photoperiod in vitro. Ability to develop additional NAT activity in the dark was low rapidly at the "subjective" time in vitro of start of the next photoperoid. The maximal NAT activity developed in the dark consisted of both photolabile and photostable components.

Acetyltransferases↗
PubMed1983

Circadian rhythm in pineal N-acetyltransferase activity: phase shifting by light pulses (II).

N-Acetyltransferase (NAT) is an enzyme whose rhythmic activity in the pineal gland and retina is thought responsible for melatonin circadian rhythms. The enzyme has properties of a circadian biological clock--its rhythm persists in constant conditions and it is precisely controlled by light and dark. Experiments are reported in which light pulses of 1 to 10 h duration were imposed on chicks during their dark-time. The effect of these pulses upon the NAT was measured and the effect of the pulses on subsequent NAT was also determined. The experiments support the conclusion that the amount and/or duration of dark-time NAT is limited. This finding is interpreted as supporting the idea that a fixed amount of some substance, an initiator, is synthesized during the subjective day.

Acetyltransferases↗
PubMed1993

Melatonin and photoperiodic time measurement: seasonal breeding in the sheep.

Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status--the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.

Animals↗
PubMed1997

Effect of various acute 60 Hz magnetic field exposures on the nocturnal melatonin rise in the adult Djungarian hamster.

Acute exposure to a 1 Gauss 60 Hz magnetic field for 15 min beginning 2 hr before darkness delays and blunts the nighttime melatonin rhythm in some but not all studies. To determine whether other exposure parameters (dose, mode, or time) influence the nocturnal melatonin rise, adult Djungarian hamsters reared in long days (16L:8D, lights off at 1000-1800 hr) were acutely exposed to a 60 Hz continuous magnetic field (15 min of 1 or 0.1 Gauss) beginning 4 hr before or 4 hr after lights off. Other hamsters were exposed to a 60 Hz intermittent magnetic field (15 or 60 min of a 1 Gauss field, 1 min on then 1 min off) between 1 and 2 hr before lights off. In sham-exposed controls, i.e., hamsters simultaneously placed in an adjacent coil system but without current, pineal and serum melatonin concentrations increased from a low baseline (1 hr after lights off) to concentrations that were typical of the nighttime peak by 3 hr after darkness. Acute exposure to the 0.1 or 1 Gauss continuous magnetic field for 15 min at either 4 hr before or 4 hr after lights off did not disrupt the nocturnal rise in pineal or serum melatonin. Similarly, onset of the melatonin rhythm was not suppressed by intermittent magnetic field exposures compared to that in sham controls. Thus, several magnetic field exposure paradigms failed to alter the rising phase of the melatonin rhythm in pineal gland content or in circulation. These findings indicate that the biological clock mechanism that mediates photoperiodic time measurement in this seasonally breeding rodent is resistant to a variety of acute continuous or intermittent magnetic field exposures.

Animals↗
PubMed1997

Melatonin site and mechanism of action: single or multiple?

By affecting the entrainment pathways of the biologic clock, melatonin has a major influence on the circadian and seasonal organization of vertebrates. In addition, a number of versatile functions that far transcend melatonin actions on photoperiodic time measurement and circadian entrainment have emerged. Melatonin is a free radical scavenger and antioxidant and it has a significant immunomodulatory activity, being presumably a major factor in an organism's defense toxic agents and invading organisms. Besides affecting specific receptors in cell membranes to exert its effects, the interaction of melatonin with nuclear receptor sites and with intracellular proteins, like calmodulin or tubulin-associated proteins, as well as the direct antioxidant effects of melatonin, may explain many general functions of the pineal hormone.

Animals↗
PubMed1998

Circadian secretion patterns of melatonin after major surgery.

Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well-known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patient's arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.

Aged↗
PubMed2006

Blue blocker glasses impede the capacity of bright light to suppress melatonin production.

Blocking morning light exposure with dark goggles can contribute to the adjustment to night work but these glasses are incompatible with driving. Recently, it was discovered that the biological clock is most sensitive to short wavelengths (blue light). Therefore, we tested the hypothesis that cutting the blue portion of the light spectrum with orange lens glasses (blue blockers) would prevent the light-induced melatonin suppression, a test broadly used as an indirect assessment of the circadian clock sensitivity. Fourteen normal subjects were exposed at night to a 60 min bright light pulse (1300 lx behind filters) between 01:00 and 02:00 hr while wearing orange lens glasses (experimental condition) or grey lens glasses (control condition). The amount of salivary melatonin change observed during the light pulse was compared with a melatonin baseline obtained the night before. Although both glasses transmitted the same illuminance (1300 lx) but at an irradiance 25% higher for the orange lens (408 microW/cm2) compared with the grey lens (327 microW/cm2), a non-significant increase of 6% (95% CI, -20% to 9%) was observed with the orange lens whereas a significant (P < 0.05) reduction of 46% (95% CI, 35-57%) was observed with the grey lens. Blue blockers represent an elegant means to prevent the light-induced melatonin suppression. Further studies are needed to show that these glasses, which are suitable for driving, could facilitate adaptation to night work.

Adult↗
PubMed2005

Nuclear import of mPER3 in Xenopus oocytes and HeLa cells requires complex formation with mPER1.

Several transcription factors with the function of setting the biological clock in vertebrates have been described. A detailed understanding of their nucleocytolasmic transport properties may uncover novel aspects of the regulation of the circadian rhythm. This assumption led us to perform a systematic analysis of the nuclear import characteristics of the different murine PER and CRY proteins, using Xenopus oocytes and HeLa cells as experimental systems. Our major finding is that nuclear import of mPER3 requires complex formation with mPER1. We further show that the nuclear localization signal (NLS) function of mPER1 and not activation of a masked NLS in mPER3 is critical for the import of the mPER1-mPER3 complex. Finally, and as previously described in other cell systems, nuclear import of mPER proteins in Xenopus oocytes correlates positively with their phosphorylation.

Active Transport, Cell Nucleus↗
PubMed1991

Metabolic correlates to pacemaker activity in the smooth muscle of guinea-pig mesotubarium.

Oxygen consumption (FO2) and lactate production (Flac) were measured during spontaneous activity in the guinea-pig mesotubarium. During spontaneous contractions FO2 increased to maximally 0.270 +/- 0.025 mumol min-1g-1 (n = 23), followed by a rapid fall immediately upon relaxation. In the relaxed period (5-15 min) between spontaneous contractions FO2 continued to slowly decrease by about 25% towards a final value of 0.150 +/- 0.01 mumol min-1g-1. Flac showed no consistent variation during the relaxed period. Ouabain (10(-6)M) produced a contracture, which was abolished by the Ca2(+)-antagonist felodipine (10(-6)M). In the presence of felodipine, addition of ouabain caused depolarization and a decrease of oxygen consumption by 21% and of lactate production by 31%. Exchange of glucose in the physiological Krebs solution for beta-hydroxybutyrate did not influence spontaneous activity, while subsequent addition of cyanide (2 mM) abolished contractions and caused a hyperpolarization of 15 mV. Blockade of ATP-dependent K+ channels by addition of glibenclamide (10(-7)M) to the relaxed muscle in this situation caused spontaneous contractile activity to reappear. In glucose-containing Krebs solution glibenclamide had no effect on the spontaneous contractile and electrical activity and contractions persisted after addition of cyanide. The relaxing and hyperpolarizing effect of pinacidil could be counteracted by addition of glibenclamide. The results suggest that a decrease in electrogenic Na+/K(+)-pump activity in the course of the relaxed period between contractions could contribute to the pacemaker behaviour. ATP-dependent K+ channels, while having little influence on the spontaneous contractile activity under normal metabolic conditions, could be activated during blockade of aerobic and anaerobic metabolism, leading to inhibition of pacemaker activity.

Adenosine Triphosphate↗
PubMed1998

Neuroimmunomodulation of aging. A program in the pineal gland.

We have investigated for 35 years the relationship between the neuroendocrine and the thymo-lymphatic, immune system. In the last decade we have shown that the pineal gland is a main adapter and fine synchronizer of environmental variables and endogenous messages into physiological modifications of basic functions. In particular the pineal gland itself seems to regulate, via circadian, night secretion of melatonin, all basic hormonal functions and also immunity. We have shown with several in vivo models that this fundamental role of the pineal gland decays during aging. Aging itself seems to be a strictly pineal-programmed event similar to growth and puberty. The continuation of our interventions with melatonin against the typical degenerative diseases of aging must be based on an accurate evaluation of its mechanisms of action. Melatonin being a ubiquitous molecule in nature, we suggest that it has acquired during evolution of the species numerous levels of activities. In fact, melatonin can be found in a large variety of cells and tissues, and bindings sites and "receptors" have been identified in many tissues and cells of the neuroendocrine and immune system. Therefore, the progressive understanding of the aging-programming role of the pineal gland also depends on studies of melatonin and its basic regulatory function. Our present studies will be described.

Aging↗