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Kiyoshi Misawa, Daiki Mochizuki, Shiori Endo, Masato Mima, Yuki Misawa, Atsushi Imai, Kazuya Shinmura, Takeharu Kanazawa, Thomas E Carey, Hiroyuki Mineta
BACKGROUND: The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer. METHODS: We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples...
September 29, 2016: Molecular Carcinogenesis
A Gajewska, M Zielinska-Gorska, E Wasilewska-Dziubinska, M Baran, G Kotarba, K Gorski
The well-recognized sensitivity of the galanin gene in the anterior pituitary gland to estrogen suggests that estrogen receptor activity may influence the galaninergic system through modulation of galanin receptor (GALR) gene expression. Here, we evaluated the following: (i) the effects of estrogen on GALR mRNA expression; (ii) the estrogen receptor subtype that is specifically involved in this activity; and (iii) the effects of progesterone in the absence or presence of estrogen on galanin concentration in anterior pituitary gland...
June 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Peng Wang, Hui Li, Swapnali Barde, Ming-Dong Zhang, Jing Sun, Tong Wang, Pan Zhang, Hanjiang Luo, Yongjun Wang, Yutao Yang, Chuanyue Wang, Per Svenningsson, Elvar Theodorsson, Tomas G M Hökfelt, Zhi-Qing David Xu
The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG)...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Miklós Sárvári, Imre Kalló, Erik Hrabovszky, Norbert Solymosi, Annie Rodolosse, Zsolt Liposits
Estradiol (E2) robustly activates transcription of a broad array of genes in the hippocampal formation of middle-aged ovariectomized rats via estrogen receptors (ERα, ERβ, and G protein-coupled ER). Selective ERβ agonists also influence hippocampal functions, although their downstream molecular targets and mechanisms are not known. In this study, we explored the effects of long-term treatment with ERβ agonist diarylpropionitrile (DPN, 0.05 mg/kg/day, sc.) on the hippocampal transcriptome in ovariectomized, middle-aged (13 month) rats...
2016: Frontiers in Cellular Neuroscience
Stephanie Constantin, Susan Wray
GnRH neurons are regulated by hypothalamic kisspeptin neurons. Recently, galanin was identified in a subpopulation of kisspeptin neurons. Although the literature thoroughly describes kisspeptin activation of GnRH neurons, little is known about the effects of galanin on GnRH neurons. This study investigated whether galanin could alter kisspeptin signaling to GnRH neurons. GnRH cells maintained in explants, known to display spontaneous calcium oscillations, and a long-lasting calcium response to kisspeptin-10 (kp-10), were used...
August 2016: Endocrinology
Eunmi Kim, Inyoung Jeong, Suhyun Kim, Hwan-Ki Kim, Dong-Won Lee, Boa Kim, Jae Young Seong, Young-Ki Bae, Jae-Ho Ryu, Hae-Chul Park
Galanin is a multifunctional neuropeptide that is implicated in the modulation of physiological processes, including nociception, cognition, feeding behavior, neuronal growth, and reproduction. The physiological effects of galanin are mediated through its interaction with three different G protein-coupled receptors, i.e., GALR1, GALR2, and GALR3. Unlike mammals, zebrafish have four different receptors for galanin, diversified from GALR1 (GAL1a and GALR1b) and GALR2 (GALR2a and GALR2b). Despite the importance of galanin in the central nervous system (CNS), no information has been reported regarding GalR2 in zebrafish CNS...
August 15, 2016: Neuroscience Letters
Michal Zalecki, Waldemar Sienkiewicz, Amelia Franke-Radowiecka, Magdalena Klimczuk, Jerzy Kaleczyc
Gastric antrum ulcerations are common disorders occurring in humans and animals. Such localization of ulcers disturbs the gastric emptying process, which is precisely controlled by the pylorus. Galanin (Gal) and its receptors are commonly accepted to participate in the regulation of inflammatory processes and neuronal plasticity. Their role in the regulation of gastrointestinal motility is also widely described. However, there is lack of data considering antral ulcerations in relation to changes in the expression of Gal and GalR1, GalR2, GalR3 receptors in the pyloric wall tissue and galaninergic intramural innervation of the pylorus...
2016: PloS One
H Y A Chan, L W Stanton
NeuroAiD, a traditional Chinese medicine widely used to treat stroke patients in China, was recently demonstrated in rodent models and in clinical trials to possess neuroregenerative and neuroprotective properties. In order to understand the mechanisms employed by NeuroAiD to bring about its neuroproliferative and neuroprotective effects, we investigated the impact of MLC901, a reformulated version of MLC601, on human neural progenitors undergoing neural differentiation at the molecular level by performing three independent microarray experiments...
October 2016: Pharmacogenomics Journal
Wen-Qi Hui, Qi Cheng, Tian-Yu Liu, Qin Ouyang
Galanin receptor type 2 (GALR2) is a class A G-protein-coupled receptor (GPCR), and it has been reported that orthosteric ligands and positive allosteric modulators (PAMs) of GALR2 could potentially be used to treat epilepsy. So far, the X-ray structure of this receptor has not been resolved, and knowledge of the 3D structure of GALR2 may prove informative in attempts to design novel ligands and to explore the mechanism for the allosteric modulation of this receptor. In this study, homology modeling was used to obtain several GALR2 models using known templates...
April 2016: Journal of Molecular Modeling
Lizan Kawa, Swapnali Barde, Ulf P Arborelius, Elvar Theodorsson, Denes Agoston, Mårten Risling, Tomas Hökfelt
The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI...
May 2016: Experimental Neurology
Arfaxad Reyes-Alcaraz, Yoo-Na Lee, Gi Hoon Son, Nam Hoon Kim, Dong-Kyu Kim, Seongsik Yun, Dong-Hoon Kim, Jong-Ik Hwang, Jae Young Seong
The novel neuropeptide spexin (SPX) was discovered to activate galanin receptor 2 (GALR2) and 3 (GALR3) but not galanin receptor 1 (GALR1). Although GALR2 is known to display a function, particularly in anxiety, depression, and appetite regulation, the further determination of its function would benefit from a more stable and selective agonist that acts only at GALR2. In the present study, we developed a GALR2-specific agonist with increased stability in serum. As galanin (GAL) showed a low affinity to GALR3, the residues in SPX were replaced with those in GAL, revealing that particular mutations such as Gln5 → Asn, Met7 → Ala, Lys11 → Phe, and Ala13 → Pro significantly decreased potencies toward GALR3 but not toward GALR2...
2016: Scientific Reports
Peter Petschner, Gabriella Juhasz, Viola Tamasi, Csaba Adori, Laszlo Tothfalusi, Tomas Hökfelt, Gyorgy Bagdy
It is widely accepted that efficacy and speed of current antidepressants' therapeutic effect are far from optimal. Thus, there is a need for the development of antidepressants with new mechanisms of action. The neuropeptide galanin and its receptors (GalR1, GalR2 and GalR3) are among the promising targets. However, it is not clear whether or not the galanin system is involved in the antidepressant effect exerted by the currently much used inhibitors of the reuptake of serotonin and/or noradrenaline. To answer this question we administered the selective serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine (40mg/kg/day via osmotic minipumps) to normal rats and examined the levels of the transcripts for galanin and GalR1-3 after a 3-week venlafaxine treatment in the dorsal raphe, hippocampus and frontal cortex...
June 2016: Neuropeptides
Carmelo Millón, Antonio Flores-Burgess, Manuel Narváez, Dasiel O Borroto-Escuela, Luis Santín, Belen Gago, José Angel Narváez, Kjell Fuxe, Zaida Díaz-Cabiale
Galanin N-terminal fragment (1-15) [GAL(1-15)] is associated with depression-related and anxiogenic-like effects in rats. In this study, we analyzed the ability of GAL(1-15) to modulate 5-HT1A receptors (5-HT1AR), a key receptor in depression. GAL(1-15) enhanced the antidepressant effects induced by the 5-HT1AR agonist 8-OH-DPAT in the forced swimming test. These effects were stronger than the ones induced by Galanin (GAL). This action involved interactions at receptor level since GAL(1-15) affected the binding characteristics and the mRNA levels of 5-HT1AR in the dorsal hippocampus and dorsal raphe...
January 20, 2016: Brain Structure & Function
Xi-Yue Zhang, Yi-Ming Zhang, Meng-Lin Zhang, Long-Chuan Yu
The present study was performed to explore the effect of the galanin receptor 2 (GalR2) antagonist M871 on the galanin-induced antinociception in periaqueductal grey (PAG), and an involvement of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in the galanin-induced antinociception. Intra-PAG injection of galanin induced marked increases in HWLs to noxious thermal and mechanical stimulation. The increased HWLs to thermal and mechanical stimulation decreased significantly after intra-PAG administration of the GalR2 antagonist M871, indicating an involvement of GalR2 in the galanin-induced antinociception in PAG of rats...
September 14, 2015: Neuroscience Letters
Zhenwen Zhang, Penghua Fang, Mingyi Shi, Yan Zhu, Ping Bo
Alzheimer's disease is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological and clinical studies demonstrated that type 2 diabetes mellitus is an important risk factor for the development of Alzheimer's disease, i.e., the patients with type 2 diabetes mellitus are frequently companied with Alzheimer's disease symptoms. Despite many studies recently probed into the comorbid state of both diseases, so far the precise mechanism for this association is poorly understood...
September 2015: Mechanisms of Ageing and Development
Takeharu Kanazawa, Kiyoshi Misawa, Yuki Misawa, Takayuki Uehara, Hirofumi Fukushima, Gen Kusaka, Mikiko Maruta, Thomas E Carey
Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor...
August 2015: Toxins
Krista Freimann, Kaido Kurrikoff, Ülo Langel
INTRODUCTION: Galanin is a 29/30 amino acid long neuropeptide that is widely expressed in the brains of many mammals. Galanin exerts its biological activities through three different G protein-coupled receptors, GalR1, GalR2 and GalR3. The widespread distribution of galanin and its receptors in the CNS and the various physiological and pharmacological effects of galanin make the galanin receptors attractive drug targets. AREAS COVERED: This review provides an overview of the role of galanin and its receptors in the CNS, the involvement of the galaninergic system in various neurological diseases and the development of new galanin receptor-specific ligands...
2015: Expert Opinion on Therapeutic Targets
Cheng-yuan Lin, Man Zhang, Tao Huang, Li-ling Yang, Hai-bo Fu, Ling Zhao, Linda L D Zhong, Huai-xue Mu, Xiao-ke Shi, Christina F P Leung, Bao-min Fan, Miao Jiang, Ai-ping Lu, Li-xin Zhu, Zhao-xiang Bian
A novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice...
2015: Scientific Reports
Falk Schrödl, Alexandra Kaser-Eichberger, Andrea Trost, Clemens Strohmaier, Barbara Bogner, Christian Runge, Daniela Bruckner, Karolina Motloch, Barbara Holub, Barbara Kofler, Herbert A Reitsamer
The neuropeptide galanin (GAL) is widely distributed within intrinsic and extrinsic sources supplying the eye. It is involved in regulation of the vascular tone, thus important for ocular homeostasis. Since the presence/distribution of its receptors is unknown, we here screen for the presence of the various GAL receptors in the human eye. Meeting the Helsinki-Declaration, human eyes (n = 6; 45-83 years of age, of both sex, post mortem time 10-19 h) were obtained from the cornea bank and prepared for immunohistochemistry against GAL receptors 1-3 (GALR1-GALR3)...
September 2015: Experimental Eye Research
Christina Springstead Scanlon, Rajat Banerjee, Ronald C Inglehart, Min Liu, Nickole Russo, Amirtha Hariharan, Elizabeth A van Tubergen, Sara L Corson, Irfan A Asangani, Charlotte M Mistretta, Arul M Chinnaiyan, Nisha J D'Silva
Perineural invasion (PNI) is an indicator of poor survival in multiple cancers. Unfortunately, there is no targeted treatment for PNI since the molecular mechanisms are largely unknown. PNI is an active process, suggesting that cancer cells communicate with nerves. However, nerve-tumour crosstalk is understudied due to the lack of in vivo models to investigate the mechanisms. Here we developed an in vivo model of PNI to characterize this interaction. We show that the neuropeptide galanin (GAL) initiates nerve-tumour crosstalk via activation of its G protein-coupled receptor, GALR2...
2015: Nature Communications
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