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https://www.readbyqxmd.com/read/28736839/the-neurotensin-nts1-receptor-agonist-pd149163-produces-antidepressant-like-effects-in-the-forced-swim-test-further-support-for-neurotensin-as-a-novel-pharmacologic-strategy-for-antidepressant-drugs
#1
Lawrence M Carey, Remington J Rice, Adam J Prus
Preclinical Research Neurotensin is a nonbrain penetrant neuropeptide neurotransmitter that alters dopaminergic and serotonergic neurotransmission. Previous animal behavioral studies have demonstrated that intra-ventral tegmental administration of neurotensin and system administration of the selective neurotensin NTS1 receptor agonist, PD149163 produce antidepressant-like effects in a forced swim test and a differential reinforcement of low rate task, respectively. The present study sought to expand upon these past findings by assessing systemic administration of PD149163 in a forced swim test, a primary antidepressant preclinical screening model, in mice...
July 24, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28729827/lateral-hypothalamic-control-of-the-ventral-tegmental-area-reward-evaluation-and-the-driving-of-motivated-behavior
#2
REVIEW
Susan M Tyree, Luis de Lecea
The lateral hypothalamus (LH) plays an important role in many motivated behaviors, sleep-wake states, food intake, drug-seeking, energy balance, etc. It is also home to a heterogeneous population of neurons that express and co-express multiple neuropeptides including hypocretin (Hcrt), melanin-concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript (CART) and neurotensin (NT). These neurons project widely throughout the brain to areas such as the locus coeruleus, the bed nucleus of the stria terminalis, the amygdala and the ventral tegmental area (VTA)...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28725181/impact-of-proestrus-on-gene-expression-in-the-medial-preoptic-area-of-mice
#3
Csaba Vastagh, Zsolt Liposits
The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that-via wiring to gonadotropin-releasing hormone (GnRH) neurons-contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28722395/salt-removal-from-microliter-sample-volumes-by-multiple-phase-microelectromembrane-extractions-across-free-liquid-membranes
#4
Pavel Kubáň
A new concept for rapid and efficient salt removal from minute volumes of saline samples is presented by using multiple phase microelectromembrane extraction (μ-EME). A disposable μ-EME unit is filled with five consecutive plugs of immiscible aqueous and organic solutions; the aqueous sample forms the central phase and is encompassed by two free liquid membranes (FLMs) and two extraction solutions. Salt cations and anions migrate in opposite directions from the sample solution on application of 300 V dc electric potential, cross the neighboring FLM, and are transferred to the corresponding extraction solution...
July 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28690201/neurotensin-receptor-1-facilitates-intracellular-and-transepithelial-delivery-of-macromolecules
#5
Joanna L Bird, Rachael Simpson, Driton Vllasaliu, Alan D Goddard
G protein-coupled receptors are expressed on the surface of eukaryotic cells and internalise in response to ligand binding. The actions of the hormone and neurotransmitter neurotensin (NT) are predominantly mediated by specific interactions with one such receptor. Neurotensin receptor 1 (NTS1), which is upregulated in a variety of cancers, including pancreatic and breast tumours. NTS1 could therefore serve as a target for selective delivery of therapeutics. This study characterised the expression of NTS1 in HEK293 cells, as well as both polarised and non-polarised intestinal epithelial Caco-2 cells...
July 6, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28686721/systemic-pd149163-a-neurotensin-receptor-1-agonist-decreases-methamphetamine-self-administration-in-dba-2j-mice-without-causing-excessive-sedation
#6
Amanda L Sharpe, Erika Varela, Michael J Beckstead
Methamphetamine (METH) is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area. Previous studies in rats suggest that neurotensin agonism decreases METH self-administration, but these studies did not examine the effect of neurotensin agonism on the pattern of self-administration or open field locomotion...
2017: PloS One
https://www.readbyqxmd.com/read/28675223/carbon-nanowalls-a-new-versatile-graphene-based-interface-for-the-laser-desorption-ionization-mass-spectrometry-detection-of-small-compounds-in-real-samples
#7
I S Hosu, M Sobaszek, M Ficek, R Bogdanowicz, H Drobecq, L Boussekey, A Barras, O Melnyk, R Boukherroub, Y Coffinier
Carbon nanowalls, vertically aligned graphene nanosheets, attract attention owing to their tunable band gap, high conductivity, high mechanical robustness, high optical absorbance and other remarkable properties. In this paper, we report for the first time the use of hydrophobic boron-doped carbon nanowalls (CNWs) for laser desorption/ionization of small compounds and their subsequent detection by mass spectrometry (LDI-MS). The proposed method offers sensitive detection of various small molecules in the absence of an organic matrix...
July 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/28649992/a-key-role-for-neurotensin-in-chronic-stress-induced-anxiety-like-behaviour-in-rats
#8
Catherine P Normandeau, Ana Paula Ventura Silva, Emily R Hawken, Staci Angelis, Calvin Sjaarda, Xudong Liu, José Miguel Pêgo, Éric C Dumont
Chronic stress is a major cause of anxiety disorders that can be reliably modeled pre-clinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviours and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the Bed Nucleus of the Stria Terminalis (BNST), a brain region suspected to contribute to anxiety disorders...
June 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28595536/neuroprotective-effects-of-drug-induced-therapeutic-hypothermia-in-central-nervous-system-diseases
#9
Junwei Ma, Yibin Wang, Zhong Wang, Haiying Li, Zhimin Wang, Gang Chen
Cerebrovascular diseases often cause neurological deficits. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is further considered in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor...
June 6, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28591806/quantitative-proteomics-of-intestinal-mucosa-from-male-mice-lacking-intestinal-epithelial-insulin-receptors
#10
Stina Rikke Jensen, Erwin M Schoof, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Thomas Kislinger, Patricia L Brubaker
The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was applied to jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28560510/the-role-of-neurotensin-as-a-novel-biomarker-in-the-endoscopic-screening-of-high-risk-population-for-developing-colorectal-neoplasia
#11
Christos Kontovounisios, Shengyang Qiu, Shahnawaz Rasheed, Ara Darzi, Paris Tekkis
Colorectal cancer screening programs aim at early detection of cancer to reduce incidence rates and mortality. The objective of this study is to identify the role of neurotensin in the endoscopic screening of high-risk population for developing colorectal neoplasia. Blood samples from patients referred for urgent colonoscopy to investigate symptoms suspicious of colorectal cancer were collected. Blood neurotensin levels were measured using enzyme-linked immunosorbent assay. Colonoscopy findings were used as reference for determining the diagnostic accuracy of blood neurotensin...
May 30, 2017: Updates in Surgery
https://www.readbyqxmd.com/read/28556374/oncogenic-role-of-neurotensin-and-neurotensin-receptors-in-various-cancers
#12
REVIEW
Qing Ouyang, Ji Zhou, Wei Yang, Hongjuan Cui, Minhui Xu, Liang Yi
Neurotensin (NTS) has long been recognized as a neurotransmitter or neuromodulator in the central nervous system and as an endocrine agent in the periphery via actions mediated through neurotensin receptors (NTSRs). Many studies support a role for NTS in the endocrine, autocrine and paracrine growth stimulation of cancer, with oncogenic actions described for NTS in different types of cancers and cancer cell lines at each step of cancer progression, ranging from tumor growth and survival to metastatic spread...
May 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28536844/evaluation-of-neurotensin-receptor-1-as-a-potential-imaging-target-in-pancreatic-ductal-adenocarcinoma
#13
Xiaoqin Yin, Mengzhe Wang, Hui Wang, Huaifu Deng, Tingting He, Yue Tan, Zehua Zhu, Zhanhong Wu, Shuo Hu, Zibo Li
Pancreatic cancer is one of the deadliest human malignancies and lack of effective diagnostic and therapeutic methods. Accumulating evidence suggests that the neurotensin (NT) and neurotensin receptors (NTRs) play key roles in pancreatic adenocarcinoma growth and survival. In this study, we not only evaluate the NTR1 expression in pancreatic cancer patient samples, but also explore the PET and fluorescence imaging of NTR1 expression in pancreatic cancer animal models. The NTR1 expression was evaluated by immunohistochemistry staining in clinical patient tissue samples with pancreatic ductal adenocarcinoma, insulinoma, and pancreatitis...
August 2017: Amino Acids
https://www.readbyqxmd.com/read/28534946/differentiation-of-nestin%C3%A2-negative-human-hair-follicle-outer-root-sheath-cells-into-neurons-in%C3%A2-vitro
#14
Wei Wu, Xiao-Li Wu, Yu-Qing Ji, Zhen Gao
A specialized quiescent population of hair follicle stem cells, residing in the hair follicle outer root sheath cells (ORSCs), has previously demonstrated pluripotency for differentiation into neural stem cells (NSCs). A previous study indicated that nestin‑positive hair follicle ORSCs are able to differentiate into neurons. However, little has been reported on the isolation of nestin‑negative human ORSCs and whether they can successfully differentiate into neurons in vitro. In the present study, nestin‑positive ORSCs were significantly reduced with a prolonged incubation time in vitro...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28522313/neurotensin-in-the-nucleus-accumbens-reverses-dopamine-supersensitivity-evoked-by-antipsychotic-treatment
#15
Alice Servonnet, Ellie-Anna Minogianis, Claude Bouchard, Anne-Marie Bédard, Daniel Lévesque, Pierre-Paul Rompré, Anne-Noël Samaha
Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28510609/spr-based-fragment-screening-with-neurotensin-receptor-1-generates-novel-small-molecule-ligands
#16
Sylwia Huber, Fabio Casagrande, Melanie N Hug, Lisha Wang, Philipp Heine, Lutz Kummer, Andreas Plückthun, Michael Hennig
The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized variants of solubilized neurotensin receptor 1 and its subsequent purification and successful structure determination presents a solid starting point to apply the approach of fragment-based screening to extend the chemical space of known neurotensin receptor 1 ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28498396/diverse-expression-patterns-and-tumorigenic-role-of-neurotensin-signaling-components-in-colorectal-cancer-cells
#17
Ji Tae Kim, Heidi L Weiss, B Mark Evers
Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28494471/inhibition-of-neurotensin-receptor-1-induces-intrinsic-apoptosis-via-let-7a-3p-bcl-w-axis-in-glioblastoma
#18
Zhen Dong, Qian Lei, Rui Yang, Shunqin Zhu, Xiao-Xue Ke, Liqun Yang, Hongjuan Cui, Liang Yi
Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored. METHODS: Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28476948/hierarchical-specification-of-pruriceptors-by-runt-domain-transcription-factor-runx1
#19
Lu Qi, Chengcheng Huang, Xiaohua Wu, Yeqi Tao, Jingjing Yan, Tianyong Shi, Cheng Cao, Lu Han, Mengsheng Qiu, Qiufu Ma, Zijing Liu, Yang Liu
The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. They express the natriuretic peptide type B (NPPB), as well as a cohort of receptors and neuropeptides that have been implicated in chronic itch manifestation, including the interleukin-31 receptor IL31ra and its co-receptor Osmr, the leuktriene receptor Cysltr2, somatostatin and neurotensin...
May 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28439124/characterisation-of-a-cell-free-synthesised-g-protein-coupled-receptor
#20
Patrick J Shilling, Fabian Bumbak, Daniel J Scott, Ross A D Bathgate, Paul R Gooley
G-protein coupled receptors are the largest family of integral membrane proteins found within the human genome. They function as receptors and modulators to a wide range of ligands and responses which are crucial for human health. GPCR study, specifically the investigation of structure and interaction to cognate ligands, is of high priority. Limitations for structural study can be traced in part, to obtaining suitable quantities of recombinant protein. We sought to address the limitations of traditional recombinant technologies by utilising an Escherichia coli based cell-free protein synthesis (CFPS) approach for production of a thermostable neurotensin receptor 1 (en2NTS1)...
April 24, 2017: Scientific Reports
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