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Birgitte Georg, Birgitte Falktoft, Jan Fahrenkrug
The neuropeptide PACAP is expressed throughout the central and peripheral nervous system where it modulates diverse physiological functions including neuropeptide gene expression. We here report that in human neuroblastoma NB-1 cells PACAP transiently induces its own expression. Maximal PACAP mRNA expression was found after stimulation with PACAP for 3h. PACAP auto-regulation was found to be mediated by activation of PACAP specific PAC1Rs as PACAP had >100-fold higher efficacy than VIP, and the PAC1R selective agonist Maxadilan potently induced PACAP gene expression...
September 30, 2016: Neuropeptides
Tando Maduna, Vincent Lelievre
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuropeptides with wide, complementary, and overlapping distributions in the central and peripheral nervous systems, where they exert important regulatory roles in many physiological processes. VIP and PACAP display a large range of biological cellular targets and functions in the adult nervous system including regulation of neurotransmission and neuroendocrine secretion and neuroprotective and neuroimmune responses...
December 2016: Journal of Neuroscience Research
Haruhiko Kanasaki, Aki Oride, Tomomi Hara, Tselmeg Mijiddorj, Unurjargal Sukhbaatar, Satoru Kyo
Gonadotropin-releasing hormone (GnRH) and gonadotropins are indispensable hormones for maintaining female reproductive functions. In a similar manner to other endocrine hormones, GnRH and gonadotropins are controlled by their principle regulators. Although it has been previously established that GnRH regulates the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)-both gonadotropins-from pituitary gonadotrophs, it has recently become clear that hypothalamic GnRH is under the control of hypothalamic kisspeptin...
2016: International Journal of Molecular Sciences
William Thomas Keenan, Alan C Rupp, Rachel A Ross, Preethi Somasundaram, Suja Hiriyanna, Zhijian Wu, Tudor C Badea, Phyllis R Robinson, Bradford B Lowell, Samer S Hattar
Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters...
September 26, 2016: ELife
Grazia Maugeri, Agata Grazia D'Amico, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert a protective role against retinal injuries, including diabetic macular edema (DME). The macular damage is induced by hyperglycemia, which damages vessels supplying blood to the retina and induces hypoxia. The microenvironmental changes stimulate the expression of hypoxia-inducible factors (HIFs), which promote the choroidal endothelial cell transmigration across the retinal pigmented epithelium (RPE) into neurosensory retina, where they proliferate into new vessels under stimulation of the vascular endothelial growth factor (VEGF)...
September 23, 2016: Journal of Cellular Physiology
Victor May, Rodney L Parsons
Our understanding of G protein coupled receptor (GPCR) mechanisms and functions have evolved considerably. Among the many conceptual realignments, GPCRs can exist in an ensemble of active microstates that have the potential to differentially engage specific downstream signaling events. Furthermore, among GPCR dynamics, GPCR internalization and vesicular trafficking are no longer solely mechanisms for desensitization, but now appreciated to form intricate endosomal signaling complexes that can potentially target second messengers to intracellular compartments with high temporal and spatial resolution...
September 23, 2016: Journal of Cellular Physiology
Eva Cernuda-Morollón, Nuria Riesco, Pablo Martínez-Camblor, Esther Serrano-Pertierra, Carmen García-Cabo, Julio Pascual
OBJECTIVE: To determine total pituitary adenylate cyclase activating polypeptide (PACAP) in peripheral blood as a potential marker of the activation of the parasympathetic arm of the trigemino-vascular system in chronic migraine (CM) in a case-control study. METHODS: Women older than 17 and diagnosed as CM were recruited. Healthy women with no headache history and women with episodic migraine (EM) served as control groups. Total PACAP and vasoactive intestinal peptide (VIP) levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before...
October 2016: Headache
Chan Lek Tan, Elizabeth K Cooke, David E Leib, Yen-Chu Lin, Gwendolyn E Daly, Christopher A Zimmerman, Zachary A Knight
Thermoregulation is one of the most vital functions of the brain, but how temperature information is converted into homeostatic responses remains unknown. Here, we use an unbiased approach for activity-dependent RNA sequencing to identify warm-sensitive neurons (WSNs) within the preoptic hypothalamus that orchestrate the homeostatic response to heat. We show that these WSNs are molecularly defined by co-expression of the neuropeptides BDNF and PACAP. Optical recordings in awake, behaving mice reveal that these neurons are selectively activated by environmental warmth...
September 22, 2016: Cell
Dominique de Seny, Gaël Cobraiville, Pierre Leprince, Marianne Fillet, Charlotte Collin, Myrielle Mathieu, Jean-Philippe Hauzeur, Valérie Gangji, Michel G Malaise
BACKGROUND: Nonunion is a failure of healing following a bone fracture. Its physiopathology remains partially unclear and the discovery of new mediators could promote the understanding of bone healing. METHODS: Thirty-three atrophic nonunion (NU) patients that failed to demonstrate any radiographic improvement for 6 consecutive months were recruited for providing serum samples. Thirty-five healthy volunteers (HV) served as the control group. Proteomics studies were performed using SELDI-TOF-MS and 2D-DIGE approaches, associated or not with Proteominer® preprocessing, to highlight biomarkers specific to atrophic nonunion pathology...
2016: Journal of Translational Medicine
Matthew M Hurley, Brian Maunze, Megan E Block, Mogen M Frenkel, Michael J Reilly, Eugene Kim, Yao Chen, Yan Li, David A Baker, Qing-Song Liu, SuJean Choi
While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability...
2016: Frontiers in Neuroscience
Anna Steinberg, Simona D Frederiksen, Frank W Blixt, Karin Warfvinge, Lars Edvinsson
BACKGROUND: Migraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG...
December 2016: Journal of Headache and Pain
Manuel Gey, Renate Wanner, Corinna Schilling, Maria T Pedro, Daniela Sinske, Bernd Knöll
Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce 'effector' RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased...
August 2016: Open Biology
A Vaczy, D Reglodi, T Somoskeoy, K Kovacs, E Lokos, E Szabo, A Tamas, T Atlasz
A number of studies have proven that pituitary adenylate cyclase activating polypeptide (PACAP) is protective in neurodegenerative diseases. Permanent bilateral common carotid artery occlusion (BCCAO) causes severe degeneration in the rat retina. In our previous studies, protective effects were observed with PACAP1-38, PACAP1-27, and VIP but not with their related peptides, glucagon, or secretin in BCCAO. All three PACAP receptors (PAC1, VPAC1, VPAC2) appear in the retina. Molecular and immunohistochemical analysis demonstrated that the retinoprotective effects are most probably mainly mediated by the PAC1 receptor...
October 2016: Journal of Molecular Neuroscience: MN
Sebastian Bardosi, Attila Bardosi, Zsuzsanna Nagy, Dora Reglodi
Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor...
October 2016: Journal of Molecular Neuroscience: MN
Timea Kvarik, Barbara Mammel, Dora Reglodi, Krisztina Kovacs, Dora Werling, Brigitta Bede, Alexandra Vaczy, Eszter Fabian, Gabor Toth, Peter Kiss, Andrea Tamas, Tibor Ertl, Judit Gyarmati, Tamas Atlasz
The oxygen-induced retinopathy (OIR) is a well-established rodent model of retinopathy of prematurity (ROP), which is one of the most common causes of childhood visual impairment affecting preterm babies. Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to have neuroprotective effects. Several studies have revealed the presence of PACAP and its receptors in the retina and reported its protective effects in ischemic and diabetic retinopathy. In this study, we investigated whether PACAP administration can influence the vascular changes in the rat OIR model...
October 2016: Journal of Molecular Neuroscience: MN
Natalia Kasica, Piotr Podlasz, Maria Sundvik, Andrea Tamas, Dora Reglodi, Jerzy Kaleczyc
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide, with known antiapoptotic functions. Our previous in vitro study has demonstrated the ameliorative role of PACAP-38 in chicken hair cells under oxidative stress conditions, but its effects on living hair cells is now yet known. Therefore, the aim of the present study was to investigate in vivo the protective role of PACAP-38 in hair cells found in zebrafish (Danio rerio) sense organs-neuromasts. To induce oxidative stress the 5-day postfertilization (dpf) zebrafish larvae were exposed to 1...
November 2016: Neurotoxicity Research
John D Tompkins, Todd A Clason, Jean C Hardwick, Beatrice M Girard, Laura A Merriam, Victor May, Rodney L Parsons
Pituitary adenylate cyclase activating polypeptide (PACAP) peptides (Adcyap1) signaling at the selective PAC1 receptor (Adcyap1r1) participates in multiple homeostatic and stress-related responses, yet the cellular mechanisms underlying PACAP actions remain to be completely elucidated. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia and as these neurons are readily accessible, this neuronal system is particularly amenable to studying PACAP modulation of ionic conductances...
August 3, 2016: American Journal of Physiology. Cell Physiology
Grazia Maugeri, Agata Grazia D'Amico, Caterina Gagliano, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Diabetic macular edema (DME), characterized by an increase of thickness in the eye macular area, is due to breakdown of the blood-retinal barrier (BRB). Hypoxia plays a key role in the progression of this pathology by activating the hypoxia-inducible factors. In the last years, various studies have put their attention on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in retinal dysfunction. However, until now, no study has investigated their protective role against the harmful combined effect of both hyperglycemia and hypoxia on outer BRB...
August 2, 2016: Journal of Cellular Physiology
Bernadett Tuka, Nikoletta Szabó, Eszter Tóth, Zsigmond Tamás Kincses, Árpád Párdutz, Délia Szok, Tamás Körtési, Teréz Bagoly, Zsuzsanna Helyes, Lars Edvinsson, László Vécsei, János Tajti
BACKGROUND: Activation of the trigeminal-autonomic reflex, involving the trigeminal ganglion, the superior salivatory nucleus and the sphenopalatine ganglion (SPG) is crucial in the pathophysiology of cluster headache (CH). Since pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is present both in the SPG and the trigeminal ganglion (TG) and its role in migraine has been described, our aim was to determine the plasma PACAP-38 levels in different phases of episodic CH (ECH)...
December 2016: Journal of Headache and Pain
S Sasaki, J Watanabe, H Ohtaki, M Matsumoto, N Murai, T Nakamachi, J Hannibal, J Fahrenkrug, H Hashimoto, H Watanabe, H Sueki, K Honda, A Miyazaki, S Shioda
BACKGROUND: Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is required. Pituitary adenylate cyclase-activating polypeptide (PACAP) exhibits pleiotropic functions that are mediated via its receptors (PAC1R, VPAC1R and VPAC2R). Although some studies suggested a role for PACAP in the skin and several exocrine glands, the effects of PACAP on the process of eccrine sweat secretion have not been examined...
July 25, 2016: British Journal of Dermatology
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