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https://www.readbyqxmd.com/read/28720396/pituitary-adenylate-cyclase-activating-polypeptide-pacap-protects-against-mitoxantrone-induced-cardiac-injury-in-mice
#1
Venkat Subramaniam, Gin Chuang, Huijing Xia, Brendan Burn, Jessica Bradley, Jerome L Maderdrut, David H Coy, Kurt J Varner
Mitoxantrone (MXT) is an androstenedione that is used to treat cancers and progressive forms of multiple sclerosis; however, its use is limited by its cardiotoxicity. Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin/growth hormone-releasing hormone/vasoactive intestinal peptide family and has many functions, including cytoprotection and immunosuppression. We tested the hypothesis that PACAP can protect against MXT-induced cardiotoxicity in mice. Female BALB/c mice were treated once weekly for 4 weeks with saline (n=14) or MXT (3mg/kg, i...
July 15, 2017: Peptides
https://www.readbyqxmd.com/read/28707585/migraine-neurogenic-inflammation-drug-development-pharmacochemical-aspects
#2
Melinda Lukács, János Tajti, Ferenc Fülöp, József Toldi, Lars Edvinsson, László Vécsei
BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP)...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28701321/pituitary-adenylate-cyclase-activating-polypeptide-pacap-drives-cardiorespiratory-responses-to-heat-stress-in-neonatal-mice
#3
Karlene T Barrett, John Andrew Daubenspeck, Richard J A Wilson
The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as a principal and rate-limiting regulator of physiological stress responses in adult rodents and has been implicated in SIDS (Sudden Infant Death Syndrome). Recent studies show that PACAP plays a role in neonatal cardiorespiratory responses to hypoxia, hypercapnia and hypothermia, but not hyperthermia, which is often associated with SIDS. Here we tested the hypothesis that, consistent with a role in SIDS, PACAP is involved in regulating the neonatal cardiorespiratory responses to severe heat...
July 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28698051/effects-of-pituitary-adenylate-cyclase-activating-polypeptide-on-small-intestinal-int-407-cells
#4
A Illes, B Opper, D Reglodi, M Kerenyi, P Czetany, A Boronkai, E Schafer, G Toth, E Fabian, G Horvath
Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide having a widespread distribution both in the nervous system and peripheral organs including the gastrointestinal tract. It has been shown to exert actions on intestinal functions, mainly affecting glandular secretion and motility. PACAP has several different effects on cell survival depending on the cell type and the applied stimulus. Its influences on small intestinal epithelial cells are not yet elucidated, therefore the aim of the present study was to investigate the effects of PACAP on intestinal epithelial cells having high turnover (INT 407) against different harmful stimuli, such as oxidative stress, in vitro hypoxia and gamma radiation...
July 4, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28686209/detailed-characterization-of-sympathetic-chain-ganglia-schg-neurons-supplying-the-skin-of-the-porcine-hindlimb
#5
Anna Kozłowska, Anita Mikołajczyk, Mariusz Majewski
It is generally known that in the skin sympathetic fibers innervate various dermal structures, including sweat glands, blood vessels, arrectores pilorum muscles and hair follicles. However, there is a lack of data about the distribution and chemical phenotyping of the sympathetic chain ganglia (SChG) neurons projecting to the skin of the pig, a model that is physiologically and anatomically very representative for humans. Thus, the present study was designed to establish the origin of the sympathetic fibers supplying the porcine skin of the hind leg, and the pattern(s) of putative co-incidence of dopamine-β-hydroxylase (DβH) with pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin (SOM), neuronal nitric oxide synthase, substance P, vasoactive intestinal peptide, neuropeptide Y (NPY), leu5-enkephalin and galanin (GAL) using combined retrograde tracing and double-labeling immunohistochemistry...
July 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28685053/pituitary-adenylate-cyclase-activating-polypeptide-attenuates-tumor-necrosis-factor-%C3%AE-induced-apoptosis-in-endothelial-colony-forming-cells
#6
Ning Bian, Gang Du, Man Fai Ip, Juan Ding, Qing Chang, Zicheng Li
Endothelial colony-forming cells (ECFCs) are important in angiogenesis and vascular proliferation. Tumor necrosis factor (TNF)-α is a significant risk factor for the development of atherosclerosis and a key proinflammatory cytokine known to induce apoptosis in endothelial cells. Pituitary adenylate cyclase-activating polypeptide (PACAP) is one of the members of the vasoactive intestinal peptide/secretin/growth hormone-releasing hormone/glucagon superfamily and exists in two biological active forms, PACAP 38 and PACAP 27...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28659785/the-impact-of-aging-on-brain-pituitary-adenylate-cyclase-activating-polypeptide-pathology-and-cognition-in-mice-and-rhesus-macaques
#7
Pengcheng Han, Megan Nielsen, Melissa Song, Junxiang Yin, Michele R Permenter, Julie A Vogt, James R Engle, Brittany N Dugger, Thomas G Beach, Carol A Barnes, Jiong Shi
Pituitary adenylate cyclase activating polypeptide (PACAP) is associated with Alzheimer's disease (AD), but its age-related effects are unknown. We chose the rhesus macaque due to its closeness to human anatomy and physiology. We examined four variables: aging, cognitive performance, amyloid plaques and PACAP. Delayed nonmatching-to-sample recognition memory scores declined with age and correlated with PACAP levels in the striatum, parietal and temporal lobes. Because amyloid plaques were the only AD pathology in the old rhesus macaque, we further studied human amyloid precursor protein (hAPP) transgenic mice...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28656976/pituitary-adenylate-cyclase-activating-peptide-in-the-bed-nucleus-of-the-stria-terminalis-mediates-stress-induced-reinstatement-of-cocaine-seeking-in-rats
#8
Olivia W Miles, Eric A Thrailkill, Anne K Linden, Victor May, Mark E Bouton, Sayamwong E Hammack
Stressors often contribute to difficulties in maintaining behavior change following a period of abstinence, and may play a significant role in drug relapse. The activation of pituitary adenylate cyclase activating peptide (PACAP) systems in the bed nucleus of the stria terminalis (BNST) mediates many consequences of chronic stressor exposure. Here we ask whether PACAP is also involved in producing reinstatement in a model of stress-induced relapse to drug taking. Rats self-administered cocaine for 1hr daily over 10 days, which was followed by 20 days of extinction training in which lever pressing no longer produced cocaine...
June 28, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28652748/pac1-receptor-adcyap1r1-genotype-and-problematic-alcohol-use-in-a-sample-of-young-women
#9
Wojciech Łukasz Dragan, Piotr M Czerski, Małgorzata Dragan
BACKGROUND: Recent studies revealed the role of the PAC1 (ADCYAP1R1) gene variability in vulnerability to posttraumatic stress disorder in women. Due to the relatively high comorbidity of posttraumatic stress disorder and substance use disorder, we hypothesized about possible associations between PAC1 gene and problematic alcohol use. METHOD: The sample studied consisted of 491 women aged 18-28 years (mean age =21.76 years; SD =1.83) and the Alcohol Use Disorders Identification Test was used to assess drinking problems...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28624212/light-triggerable-liposomes-for-enhanced-endolysosomal-escape-and-gene-silencing-in-pc12-cells
#10
Wenjie Chen, Wei Deng, Ewa M Goldys
Liposomes are an effective gene and/or drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here, we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28610473/pituitary-adenylate-cyclase-activating-polypeptide-pacap-stress-and-sex-hormones
#11
S Bradley King, Donna J Toufexis, Sayamwong E Hammack
Stressor exposure is associated with the onset and severity of many psychopathologies that are more common in women than men. Moreover, the maladaptive expression and function of stress-related hormones have been implicated in these disorders. Evidence suggests that PACAP has a critical role in the stress circuits mediating stress-responding, and PACAP may interact with sex hormones to contribute to sex differences in stress-related disease. In this review, we describe the role of the PACAP/PAC1 system in stress biology, focusing on the role of stress-induced alterations in PACAP expression and signaling in the development of stress-induced behavioral change...
June 14, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28592413/recruitment-of-endosomal-signaling-mediates-the-forskolin-modulation-of-guinea-pig-cardiac-neuron-excitability
#12
Jean C Hardwick, Todd A Clason, John D Tompkins, Beatrice M Girard, Caitlin N Baran, Laura A Merriam, Victor May, Rodney L Parsons
Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60 % of the cardiac neurons...
June 7, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28587295/postnatal-migration-of-cerebellar-interneurons
#13
REVIEW
Ludovic Galas, Magalie Bénard, Alexis Lebon, Yutaro Komuro, Damien Schapman, Hubert Vaudry, David Vaudry, Hitoshi Komuro
Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location...
June 6, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28525332/distribution-and-immunohistochemical-characteristics-of-cocaine-and-amphetamineregulated-transcript-positive-nerve-elements-in-the-pelvic-ganglia-of-the-female-pig
#14
A Zacharko-Siembida, M Matysek, R Szalak, A Radlińska, K Obszańska, M B Arciszewski
Cocaine- and amphetamine-regulated transcript (CART) peptides are widely expressed not only in the brain but also in numerous endocrine/neuroendocrine cells as well as in neurons of the peripheral nervous system. The present study investigated the distribution patterns of CART-like immunoreactivity in the pelvic plexus (PP) of the female pig. The co-expression of CART with principal neurotransmitter markers: choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), serotonin (5-HT) or biologically active neuropeptides: pituitary adenylate cyclase-activating polypeptide (PACAP), substance P (SP), calbindin was analyzed using double immunohistochemical stainings...
March 28, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28523979/pacap-promotes-matrix-driven-adhesion-of-cultured-adult-murine-neural-progenitors
#15
James A Waschek, Joseph R Cohen, Gloria C Chi, Tomasz J Proszynski, Pawel Niewiadomski
New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitor cells (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion...
May 2017: ASN Neuro
https://www.readbyqxmd.com/read/28511915/altered-ionic-currents-and-amelioration-by-igf-1-and-pacap-in-motoneuron-derived-cells-modelling-sbma
#16
Aura M Jiménez Garduño, Leon J Juárez-Hernández, María J Polanco, Laura Tosatto, Daniela Michelatti, Daniele Arosio, Manuela Basso, Maria Pennuto, Carlo Musio
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is triggered by the binding of mutant AR to its natural ligands, testosterone and dihydrotestosterone (DHT). To investigate the neuronal alterations of motor neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ expansions in the AR alter cell ionic currents...
May 10, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28506824/hypoxia-and-nicotine-effects-on-pituitary-adenylate-cyclase-activating-polypeptide-pacap-and-its-receptor-1-pac1-in-the-developing-piglet-brainstem
#17
J Huang, K A Waters, R Machaalani
Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden Infant Death Syndrome (SIDS). Two main risk factors for SIDS are prone sleeping and cigarette smoke exposure. Using piglet models of these risk factors, intermittent hypercapnic hypoxia (IHH-mimicking rebreathing in prone position) and nicotine (main reinforcing element of cigarettes), this study aimed to determine their effects on PACAP and PAC1 protein expression in the medulla...
May 12, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28490016/backup-mechanisms-maintain-pacap-vip-induced-arterial-relaxations-in-pituitary-adenylate-cyclase-activating-polypeptide-deficient-mice
#18
Ivan Ivic, Balazs D Fulop, Tamas Juhasz, Dora Reglodi, Gabor Toth, Hitoshi Hashimoto, Andrea Tamas, Akos Koller
BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide in the VIP/secretin/glucagon peptide superfamily. Two active forms, PACAP1-38 and PACAP1-27, act through G protein-coupled receptors, the PAC1 and VPAC1/2 receptors. Effects of PACAP include potent vasomotor activity. Vasomotor activity and organ-specific vasomotor effects of PACAP-deficient mice have not yet been investigated; thus, the assessment of its physiological importance in vasomotor functions is still missing...
2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28473666/the-palmitoylation-of-the-n-terminal-extracellular-cys37-mediates-the-nuclear-translocation-of-vpac1-contributing-to-its-anti-apoptotic-activity
#19
Rongjie Yu, Hongyu Liu, Xinhe Peng, Yue Cui, Suqin Song, Like Wang, Huahua Zhang, An Hong, Tianhong Zhou
VPAC1 is class B G protein-coupled receptors (GPCR) shared by pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). The first cysteine (Cys37) in the N-terminal extracellular domain of mature VPAC1 is a free Cys not involved in the formation of conserved intramolecular disulfide bonds. In order to investigate the biological role of this Cys37 in VPAC1, the wild-type VPAC1 and Cys37/Ala mutant (VPAC1-C37/A) were expressed stably as fusion proteins with enhanced yellow fluorescent protein (EYFP) respectively in Chinese hamster ovary (CHO) cells...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450265/construct-and-face-validity-of-a-new-model-for-the-three-hit-theory-of-depression-using-pacap-mutant-mice-on-cd1-background
#20
József Farkas, László Á Kovács, László Gáspár, Anna Nafz, Tamás Gaszner, Balázs Ujvári, Viktória Kormos, Valér Csernus, Hitoshi Hashimoto, Dóra Reglődi, Balázs Gaszner
Major depression is a common cause of chronic disability. Despite decades of efforts, no equivocally accepted animal model is available for studying depression. We tested the validity of a new model based on the three-hit concept of vulnerability and resilience. Genetic predisposition (hit 1, mutation of pituitary adenylate cyclase-activating polypeptide, PACAP gene), early-life adversity (hit 2, 180-min maternal deprivation, MD180) and chronic variable mild stress (hit 3, CVMS) were combined. Physical, endocrinological, behavioral and functional morphological tools were used to validate the model...
April 25, 2017: Neuroscience
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