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Biomedical subjects

V M Wiegant

Publications and source records attributed to V M Wiegant.

At least 55 records · Page 3Linked to original sources

Vagal activation in novelty-induced tachycardia during the light phase in the rat.

The effects of repeated exposure to a novel test box on cardiac and behavioral activities (locomotion, rearing, grooming, scanning, and immobility) were studied in rats tested during the dark phase ("dark" rats) or the light phase ("light" rats) of the lighting cycle, using a telemetry system for registration of ECGs during the first and fifth tests. Heart rate (HR) was used to monitor sympathetic and parasympathetic activity; the PQ interval was used to monitor parasympathetic activity. Behavior was videotaped simultaneously. In light rats, the first and fifth exposures to the test box resulted in higher increases of active behavior and HR than in dark rats, whereas the duration of the PQ interval of the ECG was increased in light rats only. This indicates that in the light phase novelty induces active behavior associated with an increase in both sympathetic and vagal outflow, whereas in the dark phase behavioral activation is predominantly associated with increased sympathetic activity, without appreciable changes in vagal outflow. In addition, light rats showed less active behavior during the fifth than during the first exposure, indicating behavioral habituation. This behavioral habituation to the test box in the light phase coincided with vagal habituation (a diminution of the PQ interval). The increase of the tachycardiac response during the fifth exposure as compared to the first exposure suggests that it is not likely that sympathetic outflow was part of the habituation process. In dark rats no behavioral or cardiac habituation was found.

Animals↗

Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression.

BACKGROUND: The aim of the study was to search for the existence of, and define, a possible relationship between performance in neuropsychological tests and baseline concentrations of plasma cortisol, vasopressin and oxytocin in medication-free patients with a major depressive episode. METHODS: Measures of depression and anxiety were obtained and a neuropsychological battery was presented. Blood for neuropeptide analysis was drawn by venepuncture at 8.00, 16.00 and 23.00 h. RESULTS: The melancholic patients performed less well on the neuropsychological battery than did the non-melancholic patients, but these differences could be accounted for by the severity of the illness. Global intellectual functioning was negatively correlated with mean baseline plasma concentrations of cortisol. Patients with high mean plasma vasopressin concentrations remembered more auditory presented words in the delayed recall test and produced more intrusions in the visual word learning list than did patients with low or normal mean plasma vasopressin concentrations. No association was found between neuropsychological performance and plasma concentrations of oxytocin. CONCLUSIONS: Our findings support the hypothesis that elevated baseline plasma cortisol concentrations are related to cognitive impairment in depressed patients and the hypothesis that the neuropeptide vasopressin independently enhances memory, directly or indirectly through increasing arousal and attention.

Adult↗

The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal-axis and the induction of excessive grooming.

1. In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH1-24 (1 microg) induced a display of excessive grooming, and increased the plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation was blocked by pretreatment with dexamethasone, indicating that the effect of the (i.c.v.) injected peptide was not caused by a peripheral effect on the adrenal cortex. 2. Doses of 1 and 3 microg of a non-selective melanocortin-3/4-receptor antagonist (SHU 9119), or of 5 and 10 microg of a selective melanocortin-4-receptor antagonist ([D-Arg8]ACTH4-10), coadministered (i.c.v.) with 1 microg ACTH1-24, inhibited the ACTH1-24-induced activation of the hypothalamus-pituitary-adrenal-axis and excessive grooming. 3. In addition, several doses of the selective melanocortin-3-receptor agonist Lys-gamma2-MSH were centrally administered, but neither neuroendocrine, nor excessive grooming responses were observed. 4. These results imply that the melanocortin-4-receptor, and not the melanocortin-3-receptor, is involved in the ACTH1-24-induced rise in plasma levels of ACTH and corticosterone, and excessive grooming.

Adrenocorticotropic Hormone↗

Presynaptic modulation of cholecystokinin release by protein kinase C in the rat hippocampus.

The role of protein kinase C (PKC) in modulating the release of the octapeptide cholecystokinin (CCK-8) was investigated in rat hippocampal nerve terminals (synaptosomes). The PKC-activating phorbol ester 4beta-phorbol 12,13-dibutyrate (beta-PDBu) dose dependently (5-5,000 nM) increased CCK-8 release in a strictly Ca2+dependent way. This effect was observed only when synaptosomes were stimulated with the K+(A) channel blocker 4-aminopyridine (4-AP; 1 mM) but not with KCl (10-30 mM). The PDBu-induced exocytosis of CCK-8 was completely blocked by the two selective PKC inhibitors chelerythrine and calphostin-C and was not mimicked by alpha-PDBu, an inactive phorbol ester. In addition, an analogue of the endogenous PKC activator diacylglycerol, oleoylacetylglycerol, dose dependently increased CCK-8 exocytosis. Beta-PDBu (50-100 nM) also stimulated the 4-AP-evoked Ca2+-dependent release of the classic transmitter GABA, which co-localizes with CCK-8 in hippocampal interneurons. As a possible physiological trigger for PKC activation, the role of the metabotropic glutamate receptor was investigated. However, the broad receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid did not stimulate, but instead inhibited, both the CCK-8 and the GABA exocytosis. In conclusion, presynaptic PKC may stimulate exocytosis of distinct types of co-localizing neurotransmitters via modulation of presynaptic K+ channels in rat hippocampus.

Animals↗

Role of calcineurin in Ca2+-induced release of catecholamines and neuropeptides.

Neurotransmission requires rapid docking, fusion, and recycling of neurotransmitter vesicles. Several of the proteins involved in this complex Ca2+-regulated mechanism have been identified as substrates for protein kinases and phosphatases, e.g., the synapsins, synaptotagmin, rabphilin3A, synaptobrevin, munc18, MARCKS, dynamin I, and B-50/GAP-43. So far most attention has focused on the role of kinases in the release processes, but recent evidence indicates that phosphatases may be as important. Therefore, we investigated the role of the Ca2+/calmodulin-dependent protein phosphatase calcineurin in exocytosis and subsequent vesicle recycling. Calcineurin-neutralizing antibodies, which blocked dynamin I dephosphorylation by endogenous synaptosomal calcineurin activity, but had no effect on the activity of protein phosphatases 1 or 2A, were introduced into rat permeabilized nerve terminals and inhibited Ca2+-induced release of [3H]noradrenaline and neuropeptide cholecystokinin-8 in a specific and concentration-dependent manner. Our data show that the Ca2+/calmodulin-dependent phosphatase calcineurin plays an essential role in exocytosis and/or vesicle recycling of noradrenaline and cholecystokinin-8, transmitters stored in large dense-cored vesicles.

Animals↗

Effects of regular moving and handling on the behavioral and physiological responses of pigs to preslaughter treatment and consequences for subsequent meat quality.

The effects of regular moving and handling during the finishing period on behavioral and physiological responses of pigs during preslaughter treatment and consequences for meat quality were studied. From the age of 10 wk onward, 144 pigs were housed in groups of four (two gilts and two castrates) and subjected to one of the following treatments. The Environment treatment allowed pigs to move freely for 8 min outside their home pen. Then the pigs were transported in a box for 2 min, and after which they were returned to their home pen. In the Handling treatment, an experimenter remained for 3 min in the pen, and whenever a pig made contact, it was gently stroked. The experimenter then walked for an additional 1 min, without attempting to pat or stroke any pigs but subsequently held each pig in a tight grip for about 5 s. This entire procedure was then repeated. A Control treatment was also included, in which the pigs were subjected to no treatment. The Environment and Handling treatments were applied twice a week at the age of 15, 17, 19, 21, and 23 wk. At 25 wk of age, pigs were transported to the abattoir. They were held unmixed in the truck and in lairage and were manually stunned. The stockmen needed significantly less time to move Environment pigs out of their pen and into the transport box. There were no differences between treatments in salivary cortisol concentrations before or after transport. Environment and Handling pigs had paler meat than Control pigs. Glycogen content at 1 h after death and water-holding capacity were lower in Environment pigs than in Control pigs, but this did not lead to a higher incidence of PSE meat. We conclude that the pigs that had experience with leaving their home pen and some of the transport conditions were much easier to handle at loading. Pigs that are easier to move are less likely to be subjected to rough handling, which implies improved welfare, and the workload for personnel at the time of marketing is reduced. Differences in meat quality due to treatment were slight.

Abattoirs↗

Recovery of function after sciatic nerve crush lesion in rats selected for diverging locomotor activity in the open field.

The relation between recovery of function following a sciatic nerve crush lesion and an individual behavioural characteristic, the locomotor activity in an open field, was investigated in rats. Ten high-active (HA) and ten low-active (LA) rats were selected from a stock of sixty male, random-bred Wistar rats, by measuring travelled distance in an open field. Subsequently, both HA and LA rats underwent an unilateral sciatic nerve crush. Recovery of motor function revealed no significant differences between both groups, whereas recovery of sensory function in HA rats was significantly more rapid than in the LA rats (P < 0.01). These observations suggest the existence of a relationship between individual behavioural characteristics, and the sensory recovery of nerve function following crush lesion in rats.

Adrenal Glands↗

Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin-releasing hormone system: combined tracing and light and electron microscopic immunocytochemical studies.

The timing and occurrence of the preovulatory luteinizing hormone (LH) surge in the female rodent are critically dependent on the integrity of the suprachiasmatic nucleus (SCN). Destruction of the SCN leads to a cessation of the ovarian cycle, whereas implantation of estrogen in ovariectomized rats results in daily LH surges. The anatomical substrate for these effects is not known. Previous studies involving lesions of the SCN have suggested the presence of a direct vasoactive intestinal polypeptide (VIP)-containing pathway to gonadotropin-releasing hormone (GnRH) neurons. To further investigate the direct connection between the SCN and the GnRH system, we have used tract-tracing with the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PhaL) in combination with an immunocytochemical staining for GnRH in light and electron microscopic studies. Small, unilateral PhaL deposits, especially when they were placed in the rostral ventrolateral portion of the SCN, revealed a bilateral projection to the preoptic area, where PhaL-immunoreactive fibers were regularly found in close apposition to GnRH neurons. Ultrastructural studies showed synaptic interaction of PhaL-containing fibers with GnRH-immunoreactive (IR) cell bodies, thus demonstrating a direct SCN-GnRH connection. Taken together, these data provide evidence for the existence of a monosynaptic pathway from the SCN to the GnRH system in the hypothalamus of the female rat. We suggest that this pathway may contain at least VIP as a putative transmitter and may play a role in the circadian regulation of the estrous cycle in the female rat.

Animals↗

Functional recovery from sciatic nerve crush lesion in the rat correlates with individual differences in responses to chronic intermittent stress.

The aim of the present study was to monitor the influence of chronic stress on functional recovery from a sciatic nerve crush lesion in the rat. Male Wistar rats underwent standard unilateral sciatic nerve crush. Subsequently, chronic stress was induced during the recovery phase using a daily 30 min shock box session where rats received three electric footshocks each session (0.5 sec, 1 mA). Reduced body weight gain, adrenal gland hypertrophy, and thymus involution indicated that the stress rats were chronically stressed. Evaluation of sensorimotor function revealed significant differences in recovery between control and stress groups. Correlational analysis of individual stress rats indicated that recovery of the walking pattern was negatively correlated with adrenal gland and medulla enlargement, thymus involution, and plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone 45 min following the final stress session. In control rats, the index of sciatic nerve function (SF index, expressed as the difference between the injured paw and the intact contralateral paw as a percentage) was significantly correlated with adrenal medulla weight only. The present study reveals that chronic intermittent footshock stress impedes sensorimotor recovery following a sciatic nerve crush lesion and that the consequences of chronic intermittent stress are individually determined. We suggest that the quality of functional locomotor recovery after nerve crush lesion is related to the adaptive capacity or coping style of the individual rat.

Adaptation, Physiological↗

Synaptic contacts between gonadotropin-releasing hormone-containing fibers and neurons in the suprachiasmatic nucleus and perichiasmatic area: an anatomical substrate for feedback regulation?

The suprachiasmatic nucleus (SCN) is critically involved in the generation and entrainment of circadian rhythms in mammalian species. Both the occurrence and the timing of the luteinizing hormone surge on the afternoon of proestrus in the female rodent are critically dependent on the integrity of the SCN. Recently, we demonstrated the presence of a monosynaptic pathway from the SCN to the gonadotropin releasing hormone (GnRH) neurons in the preoptic area. In addition, we found that interaction between the SCN and the GnRH system may be found close to the SCN, since we observed apposition of SCN efferents and GnRH fibers at the ultrastructural level in that region. The aim of the present study was to investigate the presence of synaptic contacts between GnRH fibers and structures in the SCN and surrounding perichiasmatic area (periSCN). At the light microscopical level, the immunoreactivity for GnRH showed a considerable overlap with the immunoreactivity for vasopressin and vasoactive intestinal peptide, two neuropeptides synthesized by SCN neurons. At the ultrastructural level, we demonstrated synaptic input of GnRH-containing axons on immunocytochemically unidentified structures in the SCN/peri-SCN region. The present results clearly demonstrate that the SCN and periSCN are postsynaptic targets of GnRH fibers. It is hypothesized that the GnRH input in the SCN region represents an anatomical substrate for feedback-control between these systems.

Animals↗

Inhibition of the LH surge in cyclic rats by stress is not mediated by opioids.

The effects of intravenous (iv) administration of the opioid antagonists naloxone and naltrexone on the restraint-induced suppression of the pro-estrous LH surge were studied in cyclic female rats. To minimize stress during repeated blood sampling, the rats were provided with a jugular vein cannula. Restraint stress for 6 hrs starting at t = -1 h (the onset of the LH surge being at t = 0 h) caused a suppression of LH levels (including peak height) during the period of the LH surge. Repeated naloxone injections, given 3 h (1 mg), 4 h (0.5 mg) and 5 h (0.5 mg) after the onset of the LH surge, did not affect the restraint-induced inhibition neither did pretreatment with 1 mg naloxone at t = -75 min (i.e. 15 min before application of restraint). Naltrexone (2 mg) administered at t = -15 min induced higher plasma LH levels at t = -6 min. When rats were subsequently subjected to restraint for 5 hrs starting at t = -5 min, the restraint-induced inhibition of surge levels of LH was not affected. The results indicate that withdrawal of opioid activity in cyclic female rats before the presumed onset of the LH surge results in a premature rise of LH levels. This is in accordance with the notion that LH levels prior to the surge are under tonic inhibition of endogenous opioid peptides (EOP). In addition, the data show that opioid receptor antagonism during or before application of restraint does not alter the restraint-induced suppression of the LH surge. It is therefore concluded that EOP do not mediate the inhibitory effect of restraint stress on the LH surge in cyclic rats.

Animals↗

The effects of mixing on behavior and circadian parameters of salivary cortisol in pigs.

The present study describes an experiment that was carried out to study the effects of mixing pigs once at 25 kg, preceded by transportation for 1.5 h, on the behavior and the circadian rhythmicity of salivary cortisol. The frequency of agonistic interactions was higher for mixed pigs. This was not only the case immediately after mixing, when pigs started to fight to establish a new social rank (p < 0.05), but also 5 to 6 weeks later; still more headknocks and bites towards other pigs were seen at that time among mixed pigs (p < 0.01). However, neither the basal cortisol concentration, assessed as the MESOR of the circadian rhythm of salivary cortisol, nor the amplitude of that rhythm was different between the groups.

Aggression↗

Behavioural and intestinal responses to novelty in rats selected for diverging reactivity in the open field test.

There are indications that the severity of functional gastrointestinal disturbances in humans is linked to individual coping styles. In rodents, the open field test can be used to assess individual differences in behavioural responsivity to novel challenges. Two groups of Wistar rats were selected for high (HA) and low (LA) locomotor activity in a novel open field and fitted with electrodes on the proximal colon. During subsequent exposure to a novel box, a smaller locomotor activation in LA was accompanied by a greater increase in colonic spike burst activity compared to HA rats, even though this novel stressful challenge did not result in a clear defecation response in either group. In contrast, no marked behavioural differences between HA and LA were seen in the shock prod paradigm. Although detection of divergent behavioural responsivity in HA and LA rats may depend on stimulus quality or intensity, combined use of behavioural selection and intestinal motility recording in freely moving rats may offer a model to study individual vulnerability to stress-related disturbances of intestinal function.

Action Potentials↗

Plasma levels of arginine vasopressin elevated in patients with major depression.

Mentally healthy subjects show increased plasma concentrations of the neuropeptides, arginine vasopressin (AVP) and oxytocin (OT), under conditions of stress, but data are lacking about plasma concentrations of AVP and OT in patients with major depression. We thus assessed plasma concentrations of AVP and OT in patients with major depression (n = 52) and healthy controls (n = 37). Mean plasma AVP concentrations were higher in the group of depressed patients than in controls. A subgroup of 16 patients showed very high levels of plasma AVP, but no other feature differentiating this subgroup from the other patients was found. In-patients showed higher plasma AVP levels than out-patients, and melancholic patients had higher plasma AVP levels than did nonmelancholic patients. Plasma AVP levels were slightly related to psychomotor retardation and significantly inversely to neuroticism. Patients' plasma OT concentrations had a wider range than in controls. AVP and AVP-mediated functions may be a factor in the clinical picture of depression, possibly by influencing the activity of the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗

Psychoendocrinological assessment of the menstrual cycle: the relationship between hormones, sexuality, and mood.

The role of sex hormones in sexuality and mood across the menstrual cycle was investigated. Twenty-one normal health women were followed for one menstrual cycle. Blood samples were taken frequently, and analyzed for estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone sulfate, cortisol, and sex hormone-binding globulin. A diary concerning sexual interest and behavior, and different moods, was completed daily. Although the sample was not large, a clear effect of menstrual cycle phase on levels of testosterone and the free testosterone index was demonstrated. In a preliminary screening interview, 11 of the 21 women had reported that they suffered from premenstrual complaints (PC), the other 10 had reported no complaints in the premenstrual phase (NPC). Significant differences between the two groups were established in estradiol and the estradiol-progesterone ratio, with the NPC group having higher levels of both endocrine parameters across different menstrual samples. Psychologically, a cycle effect on tension and sexual interest was demonstrated. The NPC group reported a peak in sexual interest in the premenstrual phase, whereas the PC group reported a peak in the ovulatory phase. There was a difference between the two groups in feelings of fatigue but not in other moods across the menstrual cycle. The study provides further evidence of the importance of androgen levels in women's sexuality and shows again that the relationship between menstrual cycle phase and sexuality is much clearer than between phase and mood.

Adult↗

Hormonal status and the neuroendocrine response to a novel heterotypic stressor involving subchronic noise exposure.

Despite a number of studies on noise-induced health effects, it is still unclear to what extent different neuroendocrine pathways are affected by noise exposure. Male Wistar rats were housed in sound-attenuated rooms isolated for noise from outside. Three groups of chronically cannulated rats were exposed to either background noise (+/-64 dB) only or irregular experimental white noise (90 dB, 2-22 kHz). Two protocols, with approximately the same total amount of noise but with different densities, were used: protocol N1 (180 min random noise per day for 18 days) or protocol N2 (540 min random noise per day for 8 days). Basal levels of circulating hormones (ACTH, corticosterone, prolactin and catecholamines) and plasma glucose were measured. In control animals, no significant changes in any of these parameters were observed over 18 days. Except for plasma prolactin, N1 did not induce a significant elevation in basal hormonal levels. N2 however induced significant elevation in basal prolactin, corticosterone and noradrenaline levels. At the end of the exposure period, all animals were subjected to a novel heterotypic stressor (restraint stress) to monitor differences in neuroendocrine activation (ACTH, corticosterone and prolactin). Compared to nonexposed control animals, N1 animals showed a normal ACTH and an enhanced corticosterone response, whereas N2 animals showed an increased ACTH but a normal corticosterone response. The prolactin response of both N1 and N2 animals was significantly decreased. Adrenal cell suspension experiments revealed that in noise-exposed rats both basal- and ACTH-stimulated corticosterone production were significantly increased as compared to control animals. These results indicate that chronic noise exposure at mild intensities induces subtle but significant changes in hormonal regulation.

Adrenal Glands↗

Individual responses to acute and chronic stress in pigs.

Pigs can be characterised as resistant (R) or non-resistant (NR) at an early age (1 to 2 weeks) by means of a backtest. In the test the animal is put on its back and the number of bouts of resistance is used to characterise the animal. The test is performed twice with 1 week interval and only pigs that show a consistent response in both tests are classified as either R or NR pigs. On average eighty percent of a population can be classified by this test. R and NR pigs show consistent behavioural, physiological and immunological differences when tested in various challenge test in later life. The R pigs are more sympathetically dominated and showing an active coping style (fight/flight) as described in rats and mice. The NR pigs are more para-sympathetically dominated, resembling the passive coping style (conservation/withdrawal). In intensive husbandry, breeding sows are housed individually and often tethered. After long term tethering these sows show signs of chronic stress; overreaction of the sympathetic nervous system, hypercortisolaemia and disturbed behaviour. The most common disturbed behaviour found in tethered sows is stereotyped behaviour. Most sows develop stereotypies within 1 month after first tethering. Again great differences are found in the amount of stereotypies shown between sows. Some sows spent up to 80% of their active time on this behaviour while others hardly develop stereotypies. Sows showing high levels of stereotypies manage to counteract the sympathetic overreaction caused by the chronic stress of tethering as was shown by a decrease in heart rate during bouts of stereotyped behaviour. In this view stereotypies help the animal to cope with the averse situation of tethering. However, after 8 months of tethering stereotypies are no longer effectively attenuating heart rate. The effect of stereotypies is limited to the initial phase of chronic stress when the animal is striving to regain control. When chronic stress persists stereotypies get dissociated from their effect on the sympatho-adreno-medullary system and the animal loses control.

Acute Disease↗