Jens Hannibal
University of Copenhagen, Clinical Biochemistry, Department Member
- Clinical research assosiate professor, consultant, PhD., DmSc.edit
IntroductionThe activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but... more
IntroductionThe activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks.Materials and MethodsWe enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min until 180 min (T180) after the start of the infusion.ResultsBlood samples were collected from patients with migraine (n = 19) and healthy individua...
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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide which was originally isolated from ovine hypothalamus. PACAP exists in at least two biologically active forms, PACAP-38 and PACAP-27. The aim of this study was... more
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide which was originally isolated from ovine hypothalamus. PACAP exists in at least two biologically active forms, PACAP-38 and PACAP-27. The aim of this study was to establish the distribution, localization and smooth muscle effects of PACAP-38 and PACAP-27 in the human uteroplacental unit. For this purpose we used radioimmunoassay, immunocytochemistry and in vitro studies of the effect of the peptides on smooth muscle activity. Results: By radioimmunoassay both peptides were detected throughout the uteroplacental unit. The concentrations of PACAP-27 were in general low, ranging from 16–125 of the corresponding PACAP-38 concentrations. PACAP-immunoreactivity was localized in nerve fibres of the lower segment of the pregnant uterus, but the number of PACAP-immunoreactive nerves was very clearly reduced compared to the corresponding isthmic region of non-pregnant myometrial tissue. PACAP-immunoreactive fibres were not observed in placenta or in the umbilical cord. Both PACAP-38 and PACAP-27 caused a concentration-dependent relaxation on stem villous arteries and on the intramyometrial arteries. Neither of the peptides displayed any effect on non-vascular smooth muscle specimens from the term pregnant myometrium. In conclusion the findings suggest a vasoregulator role of PACAP in the human uteroplacental unit.
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Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in many regions of the hypothalamus including the paraventricular nucleus (PVN). In this study, using well-characterized antibodies against PACAP and... more
Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in many regions of the hypothalamus including the paraventricular nucleus (PVN). In this study, using well-characterized antibodies against PACAP and corticotropin-releasing hormone (CRH), we identified numerous nerve fibers with PACAP-immunoreactivity (ir) closely apposed to CRH neurons in the medial parvocellular subdivision of the rat PVN. Electron microscopy revealed the presence of synapses
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Neuroglobin (Ngb), a neuronal specific oxygen binding heme-globin, reported to be expressed at high levels in most layers of the murine retina. Ngb's function is presently unknown, but based on its high expression level and oxygen... more
Neuroglobin (Ngb), a neuronal specific oxygen binding heme-globin, reported to be expressed at high levels in most layers of the murine retina. Ngb's function is presently unknown, but based on its high expression level and oxygen binding capabilities Ngb was proposed to function as an oxygen reservoir facilitating oxygen metabolism in highly active neurons or to function as a neuroprotectant. In the present study, we re-examined the expression pattern of Ngb in the retina using a highly validated antibody. Furthermore, intactness of retino-hypothalamic projections and the retinal expression level of Melanopsin and Tyrosine Hydroxylase were investigated in Ngb-null mice. Ngb-immunoreactivity was found in a few neurons of the ganglion cell and inner nuclear layers co-expressing Melanopsin and Tyrosine Hydroxylase, respectively. Ngb deficiency neither affected the level of Melanopsin and Tyrosine Hydroxylase proteins nor the intactness of PACAP-positive retinohypothalamic projections in the suprachiasmatic nucleus. Based on the present results, it seems unlikely that Ngb could have a major role in retinal oxygen homeostasis and neuronal survival under normal conditions. The present study suggests that a number of previously published reports have relied on antibodies with dubious specificity.
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PurposeRetinal ganglion cell (RGC) death is a common characteristic for ocular neurodegenerative diseases such as glaucoma and optic neuropathies. Recently, GPR81 agonist treatment has been identified as a key modulator of mitochondrial... more
PurposeRetinal ganglion cell (RGC) death is a common characteristic for ocular neurodegenerative diseases such as glaucoma and optic neuropathies. Recently, GPR81 agonist treatment has been identified as a key modulator of mitochondrial function and cell survival. Thus, we aimed to test whether GPR81 agonist treatment likewise promotes RGC survival and energy metabolism in retinal explants and wholemounts from mice.MethodsRetinal explants were treated with 5 mM of the GPR81 agonist, 3,5‐DHBA, for two, four, 24 & 72 hours, and compared to conditions with no treatment. Additionally, explants were also treated with 15 mM of L‐glutamate to induce toxicity and simultaneously treated with GPR81 agonist. Tissue survival was assessed through lactate dehydrogenase (LDH) viability assays. Retinal ganglion cell survival was measured in murine wholemount retinas through immunohistochemical staining (IHC). Total ATP levels were quantified through bioluminescence assays.ResultsGPR81 agonist treat...
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The circadian clock controls many aspects of physiology, but it remains undescribed whether extracellular vesicles (EVs), including exosomes, involved in cell-cell communications between tissues are regulated in a circadian pattern. We... more
The circadian clock controls many aspects of physiology, but it remains undescribed whether extracellular vesicles (EVs), including exosomes, involved in cell-cell communications between tissues are regulated in a circadian pattern. We demonstrate a 24-hour rhythmic abundance of individual proteins in small EVs using liquid chromatography–mass spectrometry in circadian-synchronized tendon fibroblasts. Furthermore, the release of small EVs enriched in RNA binding proteins was temporally separated from those enriched in cytoskeletal and matrix proteins, which peaked during the end of the light phase. Last, we targeted the protein sorting mechanism in the exosome biogenesis pathway and established (by knockdown of circadian-regulated flotillin-1) that matrix metalloproteinase 14 abundance in tendon fibroblast small EVs is under flotillin-1 regulation. In conclusion, we have identified proteomic time signatures for small EVs released by tendon fibroblasts, which supports the view that t...
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Visual changes are some of the earliest symptoms that patients with Alzheimer’s disease (AD) experience. Pathophysiological processes such as amyloid-β plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion... more
Visual changes are some of the earliest symptoms that patients with Alzheimer’s disease (AD) experience. Pathophysiological processes such as amyloid-β plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells (RGCs) have been detected in the retina of AD patients and animal models. However, little is known about the molecular processes that underlie retinal neurodegeneration in AD. The cellular architecture and constant sensory activity of the retina impose high metabolic demands. We thus hypothesized that energy metabolism might be compromised in the AD retina similarly to what has been observed in the AD brain. To address this question, we explored cellular alterations and retinal metabolic activity in the 5 × FAD mouse model of AD. We used 8-month-old female 5 × FAD mice, in which the AD-related pathology has been shown to be apparent. We observed that RGC density is selectively affected in the retina of 5 × FAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U- 13 C] glucose and analyzed tissue extracts by gas chromatography-mass spectrometry. We found that the retinas of 5 × FAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5 × FAD retinas but no changes in the expression of markers of Müller glia, the main glial cell type responsible for glutamate uptake and glutamine synthesis in the retina. These findings suggest that AD presents with metabolic alterations not only in the brain but also in the retina that may be detrimental to RGC activity and survival, potentially leading to the visual impairments that AD patients suffer.
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A circadian rhythm is an endogenously driven roughly 24-hour cycle in biochemical, physiological or behavioural processes. Circadian rhythms have been widely observed, in plants, animals, fungi and cyanobacteria. This book presents... more
A circadian rhythm is an endogenously driven roughly 24-hour cycle in biochemical, physiological or behavioural processes. Circadian rhythms have been widely observed, in plants, animals, fungi and cyanobacteria. This book presents current research from across the globe in the study of the biology, cognition and disorders associated with circadian rhythms. Topics discussed include circadian clocks and eating disorders; disruption of circadian rhythms in hypersomnia, insomnia and sleep movement disorders; circadian pacemaker in ovary and uterus during cell differentiation and apoptosis and emerging functions of heme in transcription associated with circadian rhythms. \ua9 2012 by Nova Science Publishers, Inc. All rights reserved
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Objective To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients... more
Objective To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. Results Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo ( p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) ( p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion o...
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Background In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are... more
Background In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified. Methods In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery di...
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The pituitary adenylyl cyclase-activating polypeptide PACAP-(1-38) has potent pancreatic secretory effects. We studied its immunohistochemical localization, release, and contribution to secretion induced by electrical vagus stimulation... more
The pituitary adenylyl cyclase-activating polypeptide PACAP-(1-38) has potent pancreatic secretory effects. We studied its immunohistochemical localization, release, and contribution to secretion induced by electrical vagus stimulation using isolated perfused porcine pancreas and the PACAP receptor antagonist PACAP-(6-38) (10(-7) M). PACAP was found in nerve fibers throughout the pancreas but, in particular, encircling ganglionic vasoactive intestinal polypeptide (VIP)-positive nerve cell bodies and, mostly, colocalized with VIP. Vagus stimulation caused its release. PACAP-(1-38)(4 x 10(-9) M) stimulated exocrine and endocrine secretion and released VIP. PACAP-(6-38) decreased PACAP-induced flow of juice to 59 +/- 7.8% and insulin secretion and VIP release to 12 +/- 6.8 and 57 +/- 13%, respectively. Glucagon secretion was unaffected. PACAP-(6-38) reduced vagus-stimulated flow rate to 63 +/- 7.6%, insulin and glucagon responses to 31.8 +/- 13 and 6 +/- 4%, respectively, and VIP relea...
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The concentration of pituitary adenylyl cyclase-activating polypeptide [PACAP-(1–38)] in porcine adrenal glands amounted to 14 ± 3 pmol/g tissue. PACAP immunoreactive (PACAP-IR) fibers innervated adrenal chromaffin cells (often... more
The concentration of pituitary adenylyl cyclase-activating polypeptide [PACAP-(1–38)] in porcine adrenal glands amounted to 14 ± 3 pmol/g tissue. PACAP immunoreactive (PACAP-IR) fibers innervated adrenal chromaffin cells (often co-localized with choline acetyltransferase). Subcapsular fibers traversed the cortex-innervating endocrine cells and blood vessels [some co-storing mainly calcitonin gene-related peptide but also vasoactive intestinal polypeptide (VIP)]. PACAP-IR fibers were demonstrated in the splanchnic nerves, whereas IR adrenal nerve cell bodies were absent. In isolated, vascularly perfused adrenal gland, splanchnic nerve stimulation (16 Hz) and capsaicin (10−5 M) increased PACAP-(1–38) release (1.6-fold and 6-fold respectively, P = 0.02). PACAP-(1–38) dose-dependently stimulated cortisol (2 × 10−10 M; 24-fold increase, P = 0.02) and chromogranin A fragment (2 × 10−9 M; 15-fold increase, P = 0.05) secretion. Both were strongly inhibited by the PAC1/VPAC2 receptor antagon...
Research Interests: Endocrinology, Biology, Immunohistochemistry, Medicine, Gene expression, and 15 moreIn Situ Hybridization, Biological Sciences, Neuropeptides, Internal Medicine, Epinephrine, Animals, American, Capsaicin, Norepinephrine, High Pressure Liquid Chromatography, Neurotransmitter, Adrenal glands, hydrocortisone, Medical and Health Sciences, and Nerve fibers
PURPOSE This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic... more
PURPOSE This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic chemotherapy. PATIENTS AND METHODS Of 105 assessable patients, 57 were randomized to receive nutritional counseling, and 48 to receive no nutritional counseling and consumption of an ad lib oral intake. The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances. Counseling was standardized and performed by a trained dietitian, and took place twice monthly during a 5-month period from start of chemotherapy. RESULTS Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period. There was no change in the control group. Counseling led to an insignificant increase in body weight, but triceps skinfold measurement increased signif...
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A case of scurvy during prolonged stay in hospital is presented. Symptoms and treatment of manifest scurvy and prophylactic therapy are discussed.
Research Interests: Medicine, Humans, Male, Scurvy, Length of Stay, and 2 moreClinical Sciences and Aged(Clinical Sciences and Aged)
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Purpose To evaluate optic nerve and in particular melanopsin retinal ganglion cells (mRGCs) in relation to rest‐activity rhythm in Alzheimer disease (AD).Methods Retinal nerve fiber layer (RNFL) thickness measurements by optical coherence... more
Purpose To evaluate optic nerve and in particular melanopsin retinal ganglion cells (mRGCs) in relation to rest‐activity rhythm in Alzheimer disease (AD).Methods Retinal nerve fiber layer (RNFL) thickness measurements by optical coherence tomography were performed in 21 AD and 74 age‐matched controls. Actigraphic monitoring was performed in 16 AD patients and 10 age‐matched controls. Non‐parametric methods were applied to assess interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of rest‐activity rhythm. We also performed immunohistochemical analysis of mRGCs and axonal count on optic nerve cross‐sections in 14 neuropathologically confirmed AD and 13 control post‐mortem retinas.Results OCT evaluation showed reduced average (p=0.03) and superior (p=0.005) RNFL thickness in AD patients. Actigraphic monitoring demonstrated an increased IV (p=0.04) and reduced RA (p=0.04) in AD. Furthermore, AD patients were significantly less active during the day (p=0.03...
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The endocrine body rhythms including the hypothalamic–pituitary–thyroid axis seem to be regulated by the circadian timing system, and daily rhythmicity of circulating thyroid-stimulating hormone (TSH) is well established. The circadian... more
The endocrine body rhythms including the hypothalamic–pituitary–thyroid axis seem to be regulated by the circadian timing system, and daily rhythmicity of circulating thyroid-stimulating hormone (TSH) is well established. The circadian rhythms are generated by endogenous clocks in the central brain oscillator located in the hypothalamic suprachiasmatic nucleus (SCN) as well as multiple peripheral clocks, but information on the existence and function of a thyroid clock is limited. The molecular machinery in all clock cells is composed of a number of clock genes and their gene products are connected by autoregulatory feedback loops. Here, we provide evidence for a thyroid clock in the rat by demonstrating 24-h antiphase oscillations for the mRNA of the canonical clock genes Per1 and Bmal1, which was unaffected by hypophysectomy. By immunostaining, we supported the existence of a core oscillator in the individual thyroid cells by demonstrating a daily cytoplasmatic–nuclear shuttling of...
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In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) +... more
In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low-dose metoclopramide + lorazepam + dehydrobenzperidol. Owing to the severe sedation which occurs in some patients, the dose of lorazepam should be individually adjusted.
Research Interests: Medicine, Humans, Female, Male, Anesthesia, and 12 moreLorazepam, Sedation, Nausea, Cisplatin, Aged, Middle Aged, Adult, Combination drug therapy, Regimen, Antiemetic, Vomiting, and metoclopramide
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A case of severe toxic epidermal necrolysis is described, stressing the importance of multiorgan system involvement of the disease. A possible pathogenetic mechanism involving tumor necrosis factor is discussed.
Energy and protein intake in 32 consecutive patients with small cell lung cancer was examined at initiation of cyclical chemotherapy and after 1 and 3 months. With each cycle intakes decreased in the first 2 days following chemotherapy,... more
Energy and protein intake in 32 consecutive patients with small cell lung cancer was examined at initiation of cyclical chemotherapy and after 1 and 3 months. With each cycle intakes decreased in the first 2 days following chemotherapy, but were back to pretreatment levels on the third day. Eleven of the patients lost weight in the study period. Their energy and protein intakes were lower following chemotherapy compared to pretreatment intakes and to post-therapy intakes in weight-stable patients. Pretreatment intakes did not decrease over time, either in weight-losing or in weight-stable patients.
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Research Interests: Neuroscience, Biology, Immunohistochemistry, Medicine, Macaca, and 15 moreBrain, Animals, Male, Retina, Medical Physiology, Superior Colliculus, Lateral Geniculate Nucleus, Melanopsin, Retinal Ganglion Cells, Pupillary light reflex, Comparative Neurology, Suprachiasmatic Nucleus, Neurosciences, Visual Pathways, and Cholera toxin
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Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are structurally related neuropeptides that are widely expressed in vertebrate tissues. The two neuropeptides are pleiotropic and have been... more
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are structurally related neuropeptides that are widely expressed in vertebrate tissues. The two neuropeptides are pleiotropic and have been associated with migraine pathology. Three PACAP and VIP receptors have been described: PAC1, VPAC1, and VPAC2. The localization of these receptors in relation to VIP and PACAP in migraine-relevant structures has not previously been shown in mice. In the present study, we used fluorescence immunohistochemistry, well-characterized antibodies, confocal microscopy, and three-dimensional reconstruction to visualize the distribution of PACAP, VIP, and their receptors in the basal blood vessels (circle of Willis), trigeminal ganglion, and brain stem spinal trigeminal nucleus (SP5) of the mouse CNS. We demonstrated a dense network of circularly oriented VIP fibers on the basal blood vessels. PACAP nerve fibers were fewer in numbers compared to VIP fibers a...
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Background: Progressive retinal ganglion cell (RGC) dysfunction and death are common characteristics of retinal neurodegenerative diseases. Recently, hydroxycarboxylic acid receptor 1 (HCA1R, GPR81) was identified as a key modulator of... more
Background: Progressive retinal ganglion cell (RGC) dysfunction and death are common characteristics of retinal neurodegenerative diseases. Recently, hydroxycarboxylic acid receptor 1 (HCA1R, GPR81) was identified as a key modulator of mitochondrial function and cell survival. Thus, we aimed to test whether activation of HCA1R with 3,5-Dihydroxybenzoic acid (DHBA) also promotes RGC survival and improves energy metabolism in mouse retinas. Methods: Retinal explants were treated with 5 mM of the HCA1R agonist, 3,5-DHBA, for 2, 4, 24, and 72 h. Additionally, explants were also treated with 15 mM of L-glutamate to induce toxicity. Tissue survival was assessed through lactate dehydrogenase (LDH) viability assays. RGC survival was measured through immunohistochemical (IHC) staining. Total ATP levels were quantified through bioluminescence assays. Energy metabolism was investigated through stable isotope labeling and gas chromatography-mass spectrometry (GC-MS). Lactate and nitric oxide le...
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Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and... more
Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy and 3D reconstructions, we found NPY to be expressed in GABAergic and calretinin-immunoreactive (-ir) amacrine cells of both species as well as parvalbumin-ir amacrine cells of humans. Furthermore, we identified at least two different types of medium- to wide-field NPY-ir amacrine cells. Finally, we detected likely synaptic appositions between the NPY-ir amacrine cells and melanopsin- and nonm...
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<p>The light/dark period is indicated below the X-axis in yellow/black. The same 8 animals of each genotype were used in all experiments and data are average of 5 d of activity (see also <a... more
<p>The light/dark period is indicated below the X-axis in yellow/black. The same 8 animals of each genotype were used in all experiments and data are average of 5 d of activity (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146981#sec002" target="_blank">material and methods</a>). A. Group mean (± SEM) waveform of wheel running activity of PAC1+/+ (blue line) and PAC1-/- mice (red line) during FPP at 300 lux. B. Group mean (± SEM) waveform of wheel running activity of the same animals as in A showing FAA before mealtime (indicated by light green). C. Group mean (± SEM) waveform of wheel running activity of PAC1+/+ (blue line) and PAC1 -/- mice (red line) during SPP at 300 lux. D. Group mean (± SEM) waveform of wheel running activity of the same animals as in C showing FAA before mealtime (indicated by light green). E and F correspond to A and B but at light intensity of 10 lux. G and H correspond to C and D but at light intensity of 10 lux.</p
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Hannibal J, Hsiung HM, Fahrenkrug J. Temporal phasing of locomotor activity, heart rate rhythmicity, and core body temperature is disrupted in VIP receptor 2-deficient mice. Am J Physiol Regul Integr Comp Physiol 300: R519–R530, 2011.... more
Hannibal J, Hsiung HM, Fahrenkrug J. Temporal phasing of locomotor activity, heart rate rhythmicity, and core body temperature is disrupted in VIP receptor 2-deficient mice. Am J Physiol Regul Integr Comp Physiol 300: R519–R530, 2011. First published December 22, 2010; doi:10.1152/ajpregu.00599.2010.—Neurons of the brain’s biological clock located in the hypothalamic suprachiasmatic nucleus (SCN) generate circadian rhythms of physiology (core body temperature, hormone secretion, locomotor activity, sleep/wake, and heart rate) with distinct temporal phasing when entrained by the light/dark (LD) cycle. The neuropeptide vasoactive intestinal polypetide (VIP) and its receptor (VPAC2) are highly expressed in the SCN. Recent studies indicate that VIPergic signaling plays an essential role in the maintenance of ongoing circadian rhythmicity by synchronizing SCN cells and by maintaining rhythmicity within individual neurons. To further increase the understanding of the role of VPAC2 signali...
Pituitary adenylate cyclase activating peptide (PACAP) is a novel vasoactive intestinal polypeptide-like peptide which is present in neuronal elements of a number of peripheral organs. PACAP occurs in two forms, PACAP-27 and the... more
Pituitary adenylate cyclase activating peptide (PACAP) is a novel vasoactive intestinal polypeptide-like peptide which is present in neuronal elements of a number of peripheral organs. PACAP occurs in two forms, PACAP-27 and the C-terminally extended PACAP-38, both derived from the same precursor which in addition gives rise to a structurally-related peptide, PACAP-related peptide. Using specific radioimmunoassays for PACAP-38, PACAP-27 and PACAP-related peptide we found that the three PACAP-precursor-derived peptides were present in tissue extracts from all regions of the rat female genital tract. PACAP-38 was the dominating peptide with the highest concentrations in the Fallopian tube and the ovary. Upon reverse phase high pressure liquid chromatography the immunoreactive material was found to co-elute with synthetic PACAP-38, PACAP-27 and PACAP-related peptide, respectively. By immunohistochemistry, PACAP was shown to be located in varicose nerve fibres associated with blood vess...
Research Interests: Neuroscience, Psychology, In Situ Hybridization, Immunocytochemistry, Neuropeptides, and 15 moreCGRP, Smooth muscle, HPLC, Clinical Sciences, High Pressure Liquid Chromatography, PrP, Liquid Chromatography, VIP, Bovine Serum Albumin, Neurosciences, Blood Vessel, Radioimmunoassay, Biochemistry and cell biology, Fallopian Tube, and Paediatrics and reproductive medicine
VIP/VPAC2-receptor signaling is crucial for functioning of the circadian clock in the suprachiasmatic nucleus (SCN) since the lack results in disrupted synchrony between SCN cells and altered locomotor activity, body temperature, hormone... more
VIP/VPAC2-receptor signaling is crucial for functioning of the circadian clock in the suprachiasmatic nucleus (SCN) since the lack results in disrupted synchrony between SCN cells and altered locomotor activity, body temperature, hormone secretion and heart rhythm. Endocrine glands, including the thyroid, show daily oscillations in clock gene expression and hormone secretion, and SCN projections target neurosecretory hypothalamic thyroid-stimulating hormone (TSH)-releasing hormone cells. The aim of the study was to gain knowledge of mechanisms important for regulation of the thyroid clock by evaluating the impact of VIP/VPAC2-receptor signaling. Quantifications of mRNAs of three clock genes (Per1, Per2 and Bmal1) in thyroids of wild type (WT) and VPAC2-receptor deficient mice were done by qPCR. Tissues were taken every 4th h during 24-h 12:12 light-dark (LD) and constant darkness (DD) periods, both genders were used. PER1 immunoreactivity was visualized on sections of both WT and VP...
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ABSTRACT