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https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-neuroprotective-function-in-dopamine-based-neurodegeneration-developed-in-two-parkinsonian-models
#1
G Maasz, Z Zrinyi, D Reglodi, D Petrovics, A Rivnyak, T Kiss, A Jungling, A Tamas, Z Pirger
It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents were measured before and after PACAP-treatment in both models...
December 22, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28065858/role-of-transglutaminase-2-in-pac1-receptor-mediated-protection-against-hypoxia-induced-cell-death-and-neurite-outgrowth-in-differentiating-n2a-neuroblastoma-cells
#2
Alanood S Algarni, Alan J Hargreaves, John M Dickenson
The PAC1 receptor and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 activity by the PAC1 receptor in retinoic acid-induced differentiating N2a neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. TG2 phosphorylation was monitored via immunoprecipitation and Western blotting...
January 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28057459/parabrachial-pituitary-adenylate-cyclase-activating-polypeptide-activation-of-amygdala-endosomal-extracellular-signal-regulated-kinase-signaling-regulates-the-emotional-component-of-pain
#3
Galen Missig, Linda Mei, Margaret A Vizzard, Karen M Braas, James A Waschek, Kerry J Ressler, Sayamwong E Hammack, Victor May
BACKGROUND: Chronic pain and stress-related psychopathologies, such as depression and anxiety-associated abnormalities, are mutually reinforcing; however, the neuronal circuits and mechanisms that underlie this reinforcement are still not well understood. Pituitary adenylate cyclase activating polypeptide (PACAP; Adcyap1) and its cognate PAC1 receptor (Adcyap1r1) are expressed in peripheral nociceptive pathways, participate in anxiety-related responses and have been have been linked to posttraumatic stress disorder and other mental health afflictions...
August 29, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28043808/effects-of-vpac1-activation-in-nucleus-ambiguus-neurons
#4
Florin Liviu Gherghina, Andrei Adrian Tica, Elena Deliu, Mary E Abood, G Cristina Brailoiu, Eugen Brailoiu
The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological processes. Although some sympathetic stimulatory effects of this system have been reported, its central cardiovascular regulatory properties are poorly characterized. VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces inositol 1,4,5-trisphosphate receptor-mediated Ca(2+) mobilization, membrane depolarization and activation of P/Q-type Ca(2+) channels...
December 30, 2016: Brain Research
https://www.readbyqxmd.com/read/28013034/spatiotemporal-expression-analysis-of-nuclear-estrogen-receptors-in-the-zebrafish-ovary-and-their-regulation-in-vitro-by-endocrine-hormones-and-paracrine-factors
#5
Ka-Cheuk Liu, Shuk-Wa Lau, Wei Ge
Estradiol (E2) stimulates luteinizing hormone receptor (lhcgr) expression via nuclear estrogen receptors (nERs) in the zebrafish ovary. We have demonstrated that endocrine hormones such as gonadotropin (hCG) and paracrine factors such as epidermal growth factor (EGF) and pituitary adenylate cyclase-activating peptide (PACAP) can modulate E2-induced lhcgr expression in vitro. These observations raised a question on whether these hormones and factors exert their effects via regulating the expression of nERs. In this study, we first characterized the spatiotemporal expression profiles of three nER subtypes in the zebrafish ovary, including esr1 (ERα), esr2a (ERβ2) and esr2b (ERβ1)...
December 21, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28007571/multiple-nickel-sensitive-targets-elicit-cardiac-arrhythmia-in-isolated-mouse-hearts-after-pituitary-adenylate-cyclase-activating-polypeptide-mediated-chronotropy
#6
Etienne E Tevoufouet, Erastus N Nembo, Fabian Distler, Felix Neumaier, Jürgen Hescheler, Filomain Nguemo, Toni Schneider
The pituitary adenylate cyclase-activating polypeptide (PACAP)-27 modulates various biological processes, from the cellular level to function specification. However, the cardiac actions of this neuropeptide are still under intense studies. Using control (+|+) and mice lacking (-|-) either R-type (Cav2.3) or T-type (Cav3.2) Ca(2+) channels, we investigated the effects of PACAP-27 on cardiac activity of spontaneously beating isolated perfused hearts. Superfusion of PACAP-27 (20nM) caused a significant increase of baseline heart frequency in Cav2...
December 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28003546/adenylyl-cyclase-activating-polypeptide-reduces-phosphorylation-and-toxicity-of-the-polyglutamine-expanded-androgen-receptor-in-spinobulbar-muscular-atrophy
#7
Maria Josè Polanco, Sara Parodi, Diana Piol, Conor Stack, Mathilde Chivet, Andrea Contestabile, Helen C Miranda, Patricia M-J Lievens, Stefano Espinoza, Tobias Jochum, Anna Rocchi, Christopher Grunseich, Raul R Gainetdinov, Andrew C B Cato, Andrew P Lieberman, Albert R La Spada, Fabio Sambataro, Kenneth H Fischbeck, Illana Gozes, Maria Pennuto
Spinobulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. SBMA belongs to the family of polyQ diseases, which are fatal neurodegenerative disorders mainly caused by protein-mediated toxic gain-of-function mechanisms and characterized by deposition of misfolded proteins in the form of aggregates. The neurotoxicity of the polyQ proteins can be modified by phosphorylation at specific sites, thereby providing the rationale for the development of disease-specific treatments...
December 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27959574/porcine-dorsal-root-ganglia-ovarian-neurons-are-affected-by-long-lasting-testosterone-treatment
#8
B Jana, K Palus, K Meller, J Całka
We studied the effect of testosterone overdose on the number, distribution and chemical coding of ovarian neurons in the dorsal root ganglia (DRGs) in pigs. On day 3 of the estrous cycle, the ovaries of both the control and experimental gilts were injected with retrograde tracer Fast Blue. From day 4 of the estrous cycle to the expected day 20 of the second studied cycle, the experimental gilts were injected with testosterone, while the control gilts received oil. After the completion of the protocol the Th16-L5 DRGs were collected...
December 13, 2016: Physiological Research
https://www.readbyqxmd.com/read/27957625/a-genome-wide-analysis-in-cluster-headache-points-to-neprilysin-and-pacap-receptor-gene-variants
#9
Elena Bacchelli, Maria Michela Cainazzo, Cinzia Cameli, Simona Guerzoni, Angela Martinelli, Michele Zoli, Elena Maestrini, Luigi Alberto Pini
BACKGROUND: Cluster Headache (CH) is a severe primary headache, with a poorly understood pathophysiology. Complex genetic factors are likely to play a role in CH etiology; however, no confirmed gene associations have been identified. The aim of this study is to identify genetic variants influencing risk to CH and to explore the potential pathogenic mechanisms. METHODS: We have performed a genome-wide association study (GWAS) in a clinically well-defined cohort of 99 Italian patients with CH and in a control sample of 360 age-matched sigarette smoking healthy individuals, using the Infinium PsychArray (Illumina), which combines common highly-informative genome-wide tag SNPs and exonic SNPs...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27936470/ocular-delivery-of-pacap1-27-protects-the-retina-from-ischemic-damage-in-rodents
#10
Dora Werling, Dora Reglodi, William A Banks, Therese S Salameh, Krisztina Kovacs, Timea Kvarik, Alexandra Vaczy, Laszlo Kovacs, Flora Mayer, Bese Danyadi, Emese Lokos, Andrea Tamas, Gabor Toth, Zsolt Biro, Tamas Atlasz
Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in neuronal injuries. Bilateral common carotid artery occlusion (BCCAO) causes chronic hypoperfusion-induced degeneration in the rat retina, where we proved the retinoprotective effect of intravitreal PACAP. Although this route of administration is a common clinical practice in several diseases, easier routes are clinically important. Our aim was to investigate the potential retinoprotective effects of PACAP eye drops in BCCAO-induced ischemic retinopathy...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27900577/neuroleptic-drugs-and-pacap-differentially-affect-the-mrna-expression-of-genes-encoding-pac1-vpac-type-receptors
#11
Marta Jóźwiak-Bębenista, Edward Kowalczyk
Several lines of evidence suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide playing an important role as a neuromodulator. It has been indicated that PACAP is associated with mental diseases, and that regulation of the PACAPergic signals could be a potential target for the treatment of such psychiatric states as schizophrenia. Recent studies have suggested that action of neuroleptic drugs is mediated not only by dopaminergic and serotonergic neurotransmission, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators...
November 30, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27886414/chronic-ghrelin-treatment-reduced-photophobia-and-anxiety-like-behaviors-in-ntg-induced-migraine-role-of-pituitary-adenylate-cyclase-activating-polypeptide
#12
Fereshteh Farajdokht, Shirin Babri, Pouran Karimi, Mohammad Reza Alipour, Ramin Bughchechi, Gisou Mohaddes
Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i...
November 25, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27866657/distribution-and-chemical-coding-of-sensory-neurons-innervating-the-skin-of-the-porcine-hindlimb
#13
Anna Kozłowska, Anita Mikołajczyk, Zbigniew Adamiak, Mariusz Majewski
The aim of the present study was to establish the origin and chemical phenotyping of neurons involved in skin innervation of the porcine hind leg. The dorsal root ganglia (DRGs) of the lumbar (L4-L6) and sacral (S1-S3) spinal nerves were visualized using the fluorescent tracer Fast Blue (FB). The morphometric analysis of FB-positive (FB+)neurons showed that in the L4, L5, S1 and S2 DRGs, the small-sized perikarya constituted the major population, whereas in the L6 and S3 DRGs the medium-sized cells made up the major population...
November 5, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27826748/pacap-protects-the-adolescent-and-adult-mice-brain-from-ethanol-toxicity-and-modulates-distinct-sets-of-genes-regulating-similar-networks
#14
Hélène Lacaille, Dominique Duterte-Boucher, Hubert Vaudry, Yasmine Zerdoumi, Jean-Michel Flaman, Hitoshi Hashimoto, David Vaudry
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid neuropeptide which has been shown to exert various neuroprotective actions in vitro and in vivo; however, the ability of endogenous PACAP to prevent cell death in vivo remains to be elucidated. To explore the capacity of endogenous PACAP to prevent ethanol toxicity, adolescent and adult PACAP knockout (KO) mice were injected with ethanol in a binge drinking-like manner. Biochemical analyses revealed that ethanol administration induced an increase in the production of reactive oxygen species and the activity of caspase-3 in PACAP KO mice in an age-independent manner...
November 8, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27816700/a-subnanomolar-concentration-of-pituitary-adenylate-cyclase-activating-polypeptide-pacap-pre-synaptically-modulates-glutamatergic-transmission-in-the-rat-hippocampus-acting-through-acetylcholine
#15
Valeria Pecoraro, Lara Maria Sardone, Mariangela Chisari, Flora Licata, Guido Li Volsi, Vincenzo Perciavalle, Lucia Ciranna, Lara Costa
The neuropeptide PACAP modulates synaptic transmission in the hippocampus exerting multiple effects through different receptor subtypes: the underlying mechanisms have not yet been completely elucidated. The neurotransmitter acetylcholine (ACh) also exerts a well-documented modulation of hippocampal synaptic transmission and plasticity. Since PACAP was shown to stimulate ACh release in the hippocampus, we tested whether PACAP acting through ACh might indirectly modulate glutamate-mediated synaptic transmission at a pre- and/or at a post-synaptic level...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27816547/overexpression-of-na-ca-2-exchanger-1-display-enhanced-relaxation-in-the-gastric-fundus
#16
Yasuyuki Fujimoto, Satomi Hayashi, Yasu-Taka Azuma, Kazunori Mukai, Kazuhiro Nishiyama, Satomi Kita, Ai Morioka, Hidemitsu Nakajima, Takahiro Iwamoto, Tadayoshi Takeuchi
In gastric smooth muscles, the released Ca(2+) activates the contractile proteins and Ca(2+) taken up from the cytosol cause relaxation. The Na(+)/Ca(2+) exchanger (NCX) is an antiporter membrane protein that controls Ca(2+) influx and efflux across the membrane. However, the possible relation of NCX in gastric fundus motility is largely unknown. Here, we investigated electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in smooth muscle-specific NCX1 transgenic mice (Tg)...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27793777/acute-and-chronic-triptan-exposure-neither-alters-rodent-cerebral-blood-flow-nor-worsens-ischemic-brain-injury
#17
Mirko Muzzi, Daniela Buonvicino, Francesco De Cesaris, Alberto Chiarugi
Although it is still debated whether vasoconstriction underlies migraine resolution by triptans, they are not recommended in patients at cardiovascular risk. However, relationship between stroke incidence and triptan use is unclear, and it is unknown whether acute or chronic use of these drugs worsens ischemic brain injury. To address this issue, we investigated the effect of clinically-relevant doses of the potent cerebral artery vasoconstrictor eletriptan on cerebral blood flow (CBF) and brain infarct volumes, as well as on expression of genes involved in cerebrovascular regulation...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27745706/pka-novel-pkc-isoforms-and-erk-is-mediating-pacap-auto-regulation-via-pac1r-in-human-neuroblastoma-nb-1-cells
#18
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...
December 2016: Neuropeptides
https://www.readbyqxmd.com/read/27717098/neuropeptides-shaping-the-central-nervous-system-development-spatiotemporal-actions-of-vip-and-pacap-through-complementary-signaling-pathways
#19
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
https://www.readbyqxmd.com/read/27681724/interactions-between-two-different-g-protein-coupled-receptors-in-reproductive-hormone-producing-cells-the-role-of-pacap-and-its-receptor-pac1r
#20
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
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