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D de Wied

Publications and source records attributed to D de Wied.

At least 19 recordsLinked to original sources
PubMed2005

Minor disturbances in central nervous system function in familial neurohypophysial diabetes insipidus.

Familial neurohypophysial diabetes insipidus (FNDI) is caused by a defect in vasopressin synthesis and release as a result of a heterozygous mutation in the gene for the vasopressin prohormone. The predominant characteristic of FNDI is excessive thirst and urine production. However, vasopressin not only has peripheral endocrine effects, but also regulates numerous brain functions. We investigated whether central functions are affected in FNDI, by studying neuropsychological functioning of 23 affected members (15 males, 8 females) of a large family carrying a T/G transition mutation at nucleotide 2110 (codon 116) of the vasopressin prohormone gene (Cys116Gly). The relatively large number of family members with FNDI made it possible to compare cognitive and other CNS effects in these subjects with those of family members without FNDI. Thirty-seven adult volunteers (20 males, 17 females) from the same family and 11 non-family members (2 males, 9 females) from northern part of The Netherlands were tested. The mean age of the subjects was 35+/-12 years. Of the 63 quantified neuropsychological parameters few were statistically different between the subjects with FDNI and control subjects. Memory retrieval processes and sustained attention were worse in the subjects with FDNI. Moreover, these individuals reported significantly fewer symptoms of agoraphobia and miscellaneous symptoms, and had significantly lower scores on a scale measuring anger. The performance of FNDI subjects on an auditory verbal learning test (the 15-word test learning trial) was worse, but not significantly so, than that of the subjects without FDNI. There were subjective complaints of forgetfulness and slow recalls and those were observed in daily life by non-affected family members. These moderate differences in neuropsychological performance indicate that in human FNDI parvocellular vasopressin systems that supply the brain may be less affected or give no such serious disabilities, than the magnocellular hypothalamo-neurohypophysial system that provides vasopressin for endocrine regulation of water homeostasis.

Adult↗
PubMed2002

Neuropeptides, food intake and body weight regulation: a hypothalamic focus.

Energy homeostasis is controlled by a complex neuroendocrine system consisting of peripheral signals like leptin and central signals, in particular, neuropeptides. Several neuropeptides with anorexigenic (POMC, CART, and CRH) as well as orexigenic (NPY, AgRP, and MCH) actions are involved in this complex (partly redundant) controlling system. Starvation as well as overfeeding lead to changes in expression levels of these neuropeptides, which act downstream of leptin, resulting in a physiological response. In this review the role of several anorexigenic and orexigenic (hypothalamic) neuropeptides on food intake and body weight regulation is summarized.

Body Weight↗
PubMed2001

Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of the onset of diabetes on growth in children and cell biological defects of the mutant vasopressin prohormone.

Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant trait in which expression of a mutant vasopressin prohormone reduces vasopressin production. We investigated the NP85 Cys-->Gly mutant vasopressin prohormone in a large kindred in The Netherlands. We demonstrate that growth retardation is an important early sign in two children from this kindred, which recuperates by substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of FNDI, we analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. This defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle. We hypothesize that disturbance of the endoplasmic reticulum results in dysfunction and ultimately cell death of the cells expressing the mutant prohormone. Our data support the hypothesis that FNDI is a progressive neurodegenerative disease with delayed onset of symptoms. Its treatment requires early detection of symptoms for which growth parameters are useful.

Adult↗
PubMed2000

Endogenous corticotropin-releasing hormone inhibits conditioned-fear-induced vagal activation in the rat.

The role of the endogenous corticotropin-releasing hormone (CRH) system in the regulation of heart rate, PQ interval (a measure of vagal activity), gross activity and release of adrenocorticotropic hormone (ACTH), noradrenaline and adrenaline into the blood during conditioned fear was studied in freely moving rats. Intracerebroventricular (i.c.v.) infusion of alpha-helical CRH-(9-41) (10 microgram/3 microliter), a non-selective CRH receptor antagonist, under resting conditions had no significant effect on gross activity, heart rate and PQ interval, indicating that alpha-helical CRH at this dose was devoid of agonist effects. Conditioned fear was induced by 10 min forced exposure to a cage in which the rat had experienced footshocks (5x0.5 mAx3 s) 1 day before. Conditioned-fear rats showed freezing behaviour, associated with an increase in heart rate, PQ interval, noradrenaline and adrenaline, indicating that the conditioned-fear-induced cardiac effects were the result of coactivation of the sympathetic and parasympathetic nervous system. The i.c.v. pre-treatment of rats with alpha-helical CRH significantly reduced the conditioned-fear-induced tachycardiac and ACTH response, and enhanced the increase in PQ interval, without affecting the noradrenaline and adrenaline response. These results suggest that endogenous CRH reduces the vagal response to conditioned-fear stress in rats. To test this, rats were pre-treated with atropine methyl nitrate (0.3 mg/kg, subcutaneously; s.c.), a peripherally acting cholinergic receptor antagonist. This resulted in a complete blockade of the alpha-helical CRH-induced decrease in heart rate response and increase in PQ interval. From these findings, it is concluded that endogenous CRH in the brain inhibits vagal outflow induced by emotional stress.

Adrenocorticotropic Hormone↗
PubMed2000

The role of the CRH type 1 receptor in autonomic responses to corticotropin- releasing hormone in the rat.

The involvement of the corticotropin-releasing hormone (CRH) type 1 receptor in CRH-induced cardiac responses was studied in freely moving rats. Intracerebroventricular (icv) infusion of 2 microg CRH under resting conditions resulted in a significant increase in heart rate (HR), but did not significantly affect the PQ interval of the electrocardiogram. This effect involves sympathetic nervous system (SNS) activation, since CRH-treatment resulted in a marked increase in plasma norepinephrine (NE) and epinephrine (E), and sympathetic blockade by subcutaneously injected atenolol (1 mg/kg), a beta1-selective adrenergic antagonist, completely prevented the CRH-induced tachycardia. CRH infusion after sympathetic blockade resulted in an elongation of the PQ interval, indicating CRH-induced vagal activation. Gross locomotor activity (GA) was determined to study its possible indirect effects on cardiac activity. Although CRH induced a marked increase in GA, this effect followed the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but was a direct effect of icv CRH. Treatment with CP-154,526 (icv, 10 or 25 microg), a selective CRH type 1 receptor antagonist, did not affect baseline HR, plasma NE and E, whereas it partially blocked the CRH-induced increase in HR, plasma NE and E levels. CP-154,526 treatment had no significant effects on baseline or CRH-induced changes in GA. These results indicate that CRH activates the sympathetic nervous system at least in part via the CRH type 1 receptor.

Adrenergic beta-Antagonists↗
PubMed1999

Behavioral pharmacology of neuropeptides related to melanocortins and the neurohypophyseal hormones.

Neuropeptides are peptides which affect the nervous system. They are derived from large precursor molecules. These are converted to neurohormones, neuropeptides of the "first generation", which can be further converted to neuropeptides of the "second generation". This review is a brief survey of the nervous system effects of neuropeptides derived from pro-opiomelanocortin (POMC) and the neurohypophyseal hormones. Processing of these molecules results in neuropeptides of the first and second generation which have similar, different, more selective or even opposite effects. Among those are effects on learning and memory processes, grooming, stretching and yawning, social, sexual and rewarded behavior, aging and nerve regeneration, thermoregulation, pain, sensitivity to seizures, and cardiovascular control. Results of animal studies as well as those of clinical studies suggest that these neuropeptides may be beneficial in aging, neuropathy, memory disturbances and schizophrenia. Most of these nervous system effects in animal studies were found before receptors in the nervous system for the various neuropeptides were detected. G-protein-coupled receptors for the neuropeptides of the "first generation", i.e., melanocortin receptors, opioid receptors, and neurohypophyseal hormone receptors have been found, in contrast to the receptors for neuropeptides of the "second generation", although there are indications that G-protein coupled receptors for these may be present in the brain.

Aging↗
PubMed1998

Conditioned fear-induced tachycardia in the rat: vagal involvement.

The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be used as a measure of vagal activity. Conditioned fear was induced by 10-min forced exposure to a cage in which the rat had previously experienced footshocks (5 x 0.5 mA x 3 s). In non-shocked controls, an increase in gross activity was found and a pronounced tachycardia, without changes in PQ interval. Conditioned fear rats showed immobility behaviour, associated with a less pronounced tachycardia and an increase in PQ interval. Noradrenaline was similarly increased in both groups, whereas adrenaline was increased in conditioned fear rats only. To further evaluate the role of the vagus, rats were exposed to conditioned fear after pre-treatment with atropine methyl nitrate (0.5 mg/kg, s.c.). Again, immobility was observed with a concomitant tachycardia, but without an increase in PQ interval. These results indicate that the autonomic nervous system is differentially involved in heart rate regulation in conditioned fear rats and in non-shocked controls: in non-shocked controls a predominant sympathetic nervous system activation results in an increase in heart rate, whereas in conditioned fear rats the tachycardiac response is attenuated by a simultaneous activation of sympathetic nervous system and parasympathetic nervous system.

Animals↗
PubMed1998

Plasma arginine vasopressin and motor activity in major depression.

BACKGROUND: Previously, we found that mean plasma concentrations of arginine vasopressin (AVP), but not of oxytocin (OT), were higher in depressed patients than in healthy controls. Plasma AVP concentrations were positively correlated to clinically rated psychomotor retardation. To further explore this previously reported relation we studied psychomotor retardation by means of an activity monitor, which is a more fine-focused and more objective instrument to analyze motor retardation than a clinical rating scale. METHODS: Plasma AVP and OT concentrations, and day- and nighttime wrist activity were measured in 48 in- and outpatients with major depression and 30 healthy controls during a period of 5 consecutive days and nights. RESULTS: Principal components analysis revealed three components of motor activity: motor activity during wakefulness, motor activity during sleep, and the awake/sleep time ratio. In patients and controls an inverse relationship between plasma AVP concentrations and motor activity during wakefulness was found. Patients with elevated AVP plasma levels showed increased motor activity during sleep. CONCLUSIONS: These results suggest that high plasma AVP levels are related to the clinical picture of daytime psychomotor retardation and nighttime motor activity in major depression. Mean plasma OT concentrations were not related to measures of motor activity.

Adult↗
PubMed1998

The vasopressin deficient Brattleboro rats: a natural knockout model used in the search for CNS effects of vasopressin.

Behavioral neuroscience is using more and more gene knockout techniques to produce animals with a specific deletion. These studies have their precedent in nature. A mutation may result in a limited genetic defect, as seen in the vasopressin (VP) deficiency in the Brattleboro rat. The mutation is in a single pair of autosomal loci, and the sequences of VP gene from wild-type and homozygous Brattleboro rats are identical except for a single nucleotide deletion in the second exon. The deletion results in the synthesis of an altered VP precursor that is unable to enter the secretory pathway. The genetic disturbance results in a central diabetes insipidus comparable to that found in humans. Starting with our work during the early 1970s we found that the genetic defect in the availability of VP causes deficits in central nervous system (CNS) functions. Behavioral processes from cognition to drug tolerance appeared to be disturbed by the absence of VP, but not all behaviors are affected. The specificity of the absence of VP in causing behavioral deficits is shown in many cases. However, certain deficits are due to genetic factors other than the deletion of the VP gene. The picture is further complicated by differences in testing conditions, the absence of proper controls, i.e. heterozygous and wild-type Brattleboro rats, sex, compensation phenomena, and the absence of neuropeptides co-localized with VP. Interestingly, an age dependent spontaneous shunt to a heterozygous phenotype in vasopressinergic neurons might also compensate for the disturbance. Accordingly, findings in knockout animals should be interpreted with caution. One should realize that brain functions are modulated by multiple neuropeptides and that neuropeptides possess multiple CNS effects.

Animals↗
PubMed1996

Alterations of beta-endorphin-like immunoreactivity in CSF following behavioral training using a passive avoidance procedure.

The central opioid system may have an important influence on memory processes. In view of this, the concentration of beta-endorphin-like immunoreactivity (beta-ELIR) in cerebrospinal fluid (CSF) was measured by a radioimmunoassay in rats trained in a passive avoidance procedure. The beta-ELIR in CSF was examined immediately, 2, 5, 10, and 30 min after the learning trial in which rats were exposed to footshock (0, 0.25, or 1.0 mA for 3 s). Avoidance latency and beta-ELIR in CSF were examined 24 and 120 h after the learning trial. The beta-ELIR in CSF was increased at 5 min after the learning trial in rats exposed to footshock of 0.25 mA. The beta-ELIR in CSF was elevated at 5 and 10 min, followed by a significant decrease at 30 min after the learning trial in rats exposed to a footshock of 1.0 mA. Thus, although an increase in beta-ELIR in CSF was not, the duration of the increase was, related to the shock intensity. Interestingly, a decrease followed the increase in beta-ELIR in CSF which was significant only in rats exposed to the high shock intensity. Avoidance latencies were enhanced in a shock intensity-dependent manner at both 24 and 120 h retention tests. No change in beta-ELIR in CSF was found during retention trials. The results suggest that behavioral manipulations alter beta-ELIR in CSF. An increase in beta-ELIR in CSF may be highly associated with stressful and emotional responses during behavioral training.

Animals↗
PubMed1995

A long-lasting increase and decrease in synaptic excitability in the rat lateral septum are associated with high and low shuttle box performance, respectively.

In a series of experiments with rats, using evoked field potentials, the influence of massed trial training in 2-way shuttle box avoidance and step-through passive avoidance tasks was studied on the synaptic excitability of the lateral septum (LS) neurons and on the induction of long-term potentiation in the lateral septum in vivo. The majority of rats that attained a high performance level in the shuttle box task exhibited, after the shuttle box training, a long-lasting enhancement of synaptic excitability of lateral septum neurons, whereas most of the rats with low performance in the shuttle box showed a long-lasting depression in the LS synaptic excitability. Both types of excitability changes disappeared within 24 h. Neither the first habituation session in the passive avoidance apparatus nor the subsequent one-trial learning in passive avoidance task had a marked influence on lateral septum synaptic excitability. Both high-performance and low-performance rats exhibited a long-term potentiation (LTP)-like potentiation of synaptic excitability of the lateral septum neurons after high frequency stimulation of the fimbria fibers although the amount of LTP in high performance rats was slightly higher than that in low performance animals.

Animals↗
PubMed1993

Central nervous system effects of the neurohypophyseal hormones and related peptides.

This review of the CNS effects of the neurohypophyseal hormones and related neuropeptides discusses recent data illustrating the significance of these principles in brain function, synthesis, distribution, in particular in extrahypothalamic brain structures, binding sites, and signal transduction. Binding sites for vasopressin of the vascular V1a type have been found in the CNS and there is evidence for the existence of a subtype of the antidiuretic V2 receptor in the brain. Also two types of oxytocin binding sites have been detected. One widely distributed throughout the CNS is comparable to the uterine type receptor and a sexually dimorphic slightly different type is found in the ventromedial nucleus. Vasopressin and oxytocin can be converted to highly selective C-terminal fragments as AVP-(4-9) and OXT-(4-9) and shorter fragments. Conversely they can be acetylated. This almost completely blocks intrinsic activity in bioassays for central and peripheral effects. Such modifications are a good example of the plasticity of a neuropeptide system. For a number of CNS effects of the neurohypophyseal hormones, the whole molecule is required, as it is for their endocrine effects. This is the case for the influence of vasopressin on social communication, temperature regulation, epilepsy, and barrel rotation which may be an animal model of febrile convulsions, and some aspects of the central regulation of the cardiovascular system and for oxytocin on sexual behavior, social communication, and grooming. Nonendocrine C-terminal conversion products seem to exert their effects exclusively on the brain. These neuropeptides modulate learning and memory processes, social recognition, and rewarded behavior. The neuroendocrine and neuropeptide effect of vasopressin and oxytocin and related neuropeptides often exert their CNS effects in an opposite way. Neurochemical and electrophysiological studies suggest that norepinephrine, dopamine, serotonin, and glutamate are the neurotransmitters involved in the influence of the neurohypophyseal hormones and related neuropeptides on brain function. It appears that adequate amounts of vasopressin and oxytocin to induce these effects are released at the appropriate sites of action. It is postulated that the mix of neuropeptides released in the brain in response to environmental changes qualifies the behavioral, neuroendocrine, and immune response and the response of the autonomic nervous and vegetative systems of the organism. Although various other neuropeptides, such as those colocalized in vasopressinergic and oxytocinergic neurons, those produced in pro-opiomelanocortin (POMC) systems, and others, play a role in the modulation of adaptive responses, the neurohypophyseal hormones are unique in that their production sites in the hypothalamus serve the periphery, the pituitary, and the brain.

Amino Acid Sequence↗
PubMed1993

Structure-related effects of CRF and CRF-derived peptides: dissociation of behavioral, endocrine and autonomic activity.

Two C-terminal and one N-terminal peptide fragments derived from corticotropin-releasing factor (CRF-1-41), CRF-28-41, CRF-34-41, and CRF-1-8, and the CRF receptor antagonist alpha-helical CRF-9-41 (alpha hCRF) were evaluated for their behavioral, endocrine and autonomic nervous effects in rats. To this purpose, three different approaches were used. First, rats were tested in a passive avoidance behavioral (PAB) task after intracerebroventricular (i.c.v.) injection the peptides at five different doses. I.c.v. CRF-1-41 was found to attenuate PAB. The effects of CRF-1-41 on PAB were completely antagonized by i.c.v. pretreatment with alpha hCRF. When given as a sole treatment, the antagonist produced a bimodal effect on PAB. At low doses, alpha hCRF tended to facilitate PAB, while high doses of the antagonist significantly attenuated PAB. Both CRF fragments showed behavioral effects similar to CRF-1-41. Of all peptides tested, CRF-34-41 was found to most attenuate PAB at both retention tests. In a second experiment, the behaviorally most potent fragment CRF-34-41 was compared to CRF-1-41 for its adrenocorticotropic activity after iv injection in pentobarbital-anesthetized rats. Treatment with CRF-1-41, in a dose-related fashion, produced a significant rise in plasma ACTH, whereas CRF-34-41 was without effect. Finally, the effect of i.c.v. injected CRF-1-41 and CRF fragments on heart rate (HR) and gross activity was measured in conscious rats in their home cages during a 60-min period, using a wireless telemetry system. Concomitantly, the occurrence of grooming behavior was recorded. During the first 10 min after i.c.v. treatment, of all peptides tested, CRF-34-41 produced the most marked increase in HR, which remained significant only during the first 30 min of recording. CRF-28-41 induced a non significant transient tachycardia. The parent molecule CRF-1-41 also induced an immediate, significant tachycardia but this effect lasted longer than 60 min. The N-terminal CRF-1-8 remained without effect. No significant effects on gross activity were observed with the two short C-terminal peptides, whereas i.c.v. injected CRF-1-41 induced excessive grooming behavior. A significant grooming response was also recorded in rats given CRF-34-41 fragment, but not in those treated with CRF-28-41 or CRF-1-8.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Analysis of proopiomelanocortin (POMC) messenger ribonucleic acid and POMC-derived peptides in human peripheral blood mononuclear cells: no evidence for a lymphocyte-derived POMC system.

A number of recent studies suggest that cells of the immune system, e.g. peripheral blood mononuclear cells (PBMC), can synthesize and process POMC and secrete POMC-derived peptides, such as ACTH and endorphins, upon immune and hormonal challenges. From this, it has been proposed that POMC-derived peptides originating from lymphoid cells can function as hormones, for instance in a lymphoid-adrenal axis. In view of the important physiological implications of this proposal, the present study was designed to investigate the expression of the POMC gene in human PBMC and the production by these cells of alpha-, beta-, and gamma-endorphins (alpha E, beta E, and gamma E) peptides that are established end products of the posttranslational processing of POMC. PBMC of individual donors were used uncultured (fresh cells) or cultured for 24 and 48 h in the presence and absence of Concanavalin-A (Con-A), bacterial lipopolysaccharide, phytohemagglutinin, or CRH, and vasopressin, conditions that reportedly stimulate POMC activity in those cells, to investigate the presence of POMC transcripts by analysis of total RNA with Northern blotting and the reverse transcriptase polymerase chain reaction (RT-PCR). Large scale preparations containing over 10(9) cells (fresh, cultured with and without Con-A) originating from several donors were examined for the presence of POMC transcripts by analysis of poly(A)+ RNA on Northern blots and for the presence of alpha E, beta E, and gamma E by gel filtration over Sephadex G-75 and reverse phase HPLC, followed by assay of the fractions in four endorphin RIA systems with different specificities. On the Northern blots of total RNA, no POMC transcripts were detectable. In poly(A)+ RNA preparations, no full-length POMC mRNA was found, and it was estimated that the concentration of POMC mRNA, if present, was below approximately 0.005 transcript/cell in Con-A-stimulated cells and still lower in unstimulated cells. In accord with literature data, an 800- to 900-nucleotide POMC transcript was detected in cultured PBMC, and the levels of this transcript were stimulated by Con-A. In all samples analyzed with RT-PCR, a transcript spanning most of exons 2 and 3 was detectable only on Southern blots of the RT-PCR product, but not on agarose gels stained with ethidium bromide. Chromatographic analysis of endorphin immunoreactivities in cell extracts revealed no qualitative differences between the immunoreactive profiles of fresh PBMC or PBMC cultured with or without Con-A.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗