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Juan Li, Yang Du, Zhenqi Jiang, Yuchen Tian, Nianxiang Qiu, Yinjie Wang, Muhammad Zubair Lqbal, Menying Hu, Ruifen Zou, Lijia Luo, Shiyu Du, Jie Tian, Aiguo Wu
Due to the molecular and cellular heterogeneity of glioma, discovery of novel targeted sites and ligands for glioma imaging and therapy remains challenging. Neuropeptide Y (NPY) Y1 receptors (Y1 Rs) are highly over expressed in various brain tumors including glioma, and can serve as potential targeting sites for glioma imaging and therapy. Here, we show by in vivo fluorescent imaging that a highly selective Y1 R ligand, [Asn6 , Pro34 ] NPY (AP-NPY), facilitated circumvention of the blood brain barrier (BBB) by nanomicelles specifically targeting glioma...
March 15, 2018: Nanoscale
Liisa Ailanen, Natalia N Bezborodkina, Laura Virtanen, Suvi T Ruohonen, Anastasia V Malova, Sergey V Okovityi, Elizaveta Y Chistyakova, Eriika Savontaus
Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPYD βH ) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance...
April 2018: Pharmacology Research & Perspectives
Hussain N Alhamami, Md Main Uddin, A S M Hasan Mahmood, Karen P Briski
The hypothalamic energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK), an important regulator of counter-regulatory responses to hypoglycemia, responds to pharmacological manipulation of hindbrain AMPK activity. Dorsomedial hindbrain A2 noradrenergic neurons express hypoglycemia-sensitive metabolo-sensory biomarkers, including AMPK. Here, adult male rats were pretreated by intra-caudal fourth ventricular administration of the selective neurotoxin 6-hydroxydopamine (6-OHDA) to determine if catecholamine signaling from the aforesaid site governs hypothalamic AMPK activation during insulin-induced hypoglycemia (IIH)...
March 10, 2018: Neuroscience
Kharen L Doyle, Carla Cunha, Yvonne Hort, Ramon Tasan, Günther Sperk, John Shine, Herbert Herzog
The mouse olfactory neuroepithelium (ON) is comprised of anatomically distinct populations of cells in separate regions; apical (sustentacular and microvillar), neuronal (olfactory sensory neurons) and basal (horizontal and globose basal cells). The existence of microvillar cells (MVCs) is well documented but their nature and function remains unclear. An important transcription factor for the differentiation of MVCs is Skn-1a, with loss of function of Skn-1a in mice resulting in a complete loss of Trpm-5 expressing MVCs, while olfactory sensory neuron differentiation is normal...
March 1, 2018: Neuropeptides
Brandon Kar Meng Choo, Uday P Kundap, Yatinesh Kumari, Seow-Mun Hue, Iekhsan Othman, Mohd Farooq Shaikh
Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus , is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O...
2018: Frontiers in Pharmacology
Natalie K Y Wee, Ronaldo F Enriquez, Amy D Nguyen, Harry Horsnell, Rishikesh Kulkarni, Ee Cheng Khor, Herbert Herzog, Paul A Baldock
OBJECTIVE: To determine whether age and neuropeptide Y (NPY) were involved in the skeletal response to extended periods of diet-induced obesity. METHODS: Male wild-type (WT) and NPY null (NPYKO) mice were fed a mild (23% fat) high-fat diet for 10 weeks from 6 or 16 weeks of age. Metabolism and bone density were assessed during feeding. Skeletal changes were assessed by microCT and histomorphometry. RESULTS: High-fat feeding in 6-week-old WT mice led to significantly increased body weight, adiposity and serum leptin levels, accompanied with markedly suppressed cortical bone accrual...
March 9, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Warren Pan, Jessica M Adams, Margaret B Allison, Christa Patterson, Jonathan N Flak, Justin Jones, Garth Strohbehn, James Trevaskis, Christopher J Rhodes, David P Olson, Martin G Myers
The adipocyte-derived hormone, leptin, acts via its receptor (LepRb) on central nervous system neurons to communicate the repletion of long-term energy stores, to decrease food intake and promote energy expenditure. We generated mice that express cre recombinase from the calcitonin receptor (Calcr) locus (Calcrcre mice) to study Calcr-expressing LepRb (LepRbCalcr) neurons, which reside predominantly in the arcuate nucleus (ARC). Calcrcre-mediated ablation of LepRb in LepRbCalcrKO mice caused hyperphagic obesity...
March 7, 2018: Endocrinology
Danny Jazmati, Ute Neubacher, Klaus Funke
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is able to modify cortical excitability. Rat rTMS studies revealed a modulation of inhibitory systems, in particular that of the parvalbumin-expressing (PV+) interneurons, when using intermittent theta-burst stimulation (iTBS). OBJECTIVE: The potential disinhibitory action of iTBS raises the questions of how neocortical circuits stabilize excitatory-inhibitory balance within a physiological range. Neuropeptide Y (NPY) appears to be one candidate...
February 24, 2018: Brain Stimulation
Guoqing Wang, Mark A Cline, Elizabeth R Gilbert
The goal of this research was to determine the effect of dietary macronutrient composition on peripheral neuropeptide Y (NPY)-induced changes in adipose tissue dynamics in chicks. Chicks were fed one of three isocaloric diets from the day of hatch: high carbohydrate (HC), high fat (HF), or high protein (HP). On day 4 post-hatch, 0 (vehicle), 60, or 120 µg/kg BW of NPY was injected intraperitoneally, and subcutaneous, clavicular and abdominal adipose tissue samples were collected at 1 and 3 h post-injection...
March 3, 2018: General and Comparative Endocrinology
Daniel L Clark, Janet L McCormick, Sandra G Velleman
Neuropeptide Y (NPY) is an appetite stimulating peptide released from the central nervous system and impacts the function of many different cell types. A recent transcriptome study showed that NPY expression was altered when turkey breast muscle satellite cells were incubated at low or high temperatures, suggesting NPY may mediate temperature effects on satellite cells. However, to date minimal information exists describing the expression and function of NPY in satellite cells. The objective of this study was to determine how temperature impacts NPY and NPY receptor gene expression in satellite cells isolated from turkeys and chickens with differing genetic lineages...
March 2, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Thangaraj Anand, Ashok S K Kumar, Suban K Sahoo
An easy to prepare novel vitamin B6 cofactor derivative 3-hydroxy-N'-((3 hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)-2-naphthohydrazide (NPY) was synthesized by a one pot condensation reaction of pyridoxal with 3-hydroxy-2-naphthoic hydrazide and applied for the optical detection of Zn2+ and cysteine in the aqueous DMSO medium. The addition of Zn2+ ions leads to a selective blue-shift in the fluorescence emission spectrum of NPY from 530 nm to 475 nm, which allowed ratiometric detection of Zn2+ ions down to 8...
March 5, 2018: Photochemical & Photobiological Sciences
Abdulkerim Kasım Baltaci, Rasim Mogulkoc
Background Melatonin, an important neurohormone released from the pineal gland, is generally accepted to exercise an inhibitor effect on the thyroid gland. Zinc mediates the effects of many hormones and is found in the structure of numerous hormone receptors. Aim The present study aims to examine the effect of melatonin supplementation and pinealectomy on leptin, neuropeptide Y (NPY), melatonin and zinc levels in rats with hypothyroidism and hyperthyroidism. Methods This study was performed on the 70 male rats...
March 2, 2018: Hormone Molecular Biology and Clinical Investigation
Philippe A Melas, Peter Guban, Md Shafiqur Rahman, Catharina Lavebratt, Yvonne Forsell
The heritability of the Five-Factor Model (FFM) of human personality is high, but few genes have been identified to underlie FFM traits. Neuropeptide Y (NPY) is a pleiotropic gene implicated in stress resilience that contains two well-studied functional SNPs: (1) rs16147, which lies in the NPY promoter and affects expression levels, and (2) rs16139, which lies in the coding sequence of NPY's precursor peptide, pre-pro NPY, and affects precursor processing. In the present study we examined whether these two polymorphisms are associated with FFM traits, using a Swedish cohort (rs16147, N = 2113; and rs16139, N = 1971), and found a significant association with rs16139...
February 21, 2018: Psychiatry Research
D Hesk, D Koharski, P McNamara, P Royster, S Saluja, V Truong, K Voronin
SCH 430765 and SCH 500496 are potent and selective antagonists of the NPY5 receptor. NPY5 receptor antagonists have the potential for the treatment of obesity. [35 S]SCH 500946 was prepared for a competition binding assay which led to the identification of SCH 430765. Three distinct isotopically labelled forms of SCH 430765 were synthesized. [3 H]SCH 430765 was prepared for a preliminary ADME evaluation of the compound and [14 C]SCH 430765 for more definitive ADME work. In addition [13 C2, 2 H4 ]SCH 430765 was prepared as an internal standard for a LC-MS bioanalytical method...
March 1, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
Ramamoorthy Ramasubramanian, Karunanithi Anandababu, Mukesh Kumar, Ramasamy Mayilmurugan
Diketone substrate bound nickel(ii) complexes of 2,6-bis(1-methylbenzimidazolyl)pyridine have been synthesized and characterized as relevant active site models for unusual diketone cleaving Ni(ii)-dependent enzymes Ni-ARD and DKDO. The average Ni-Npy/benzim bond distances (2.050-2.107 Å) of model complexes are almost identical to the Ni-NHis bond distances of NiII -ARD (2.02-2.19 Å). The reaction of these adducts with dioxygen exhibited C-C cleavage with the rate of kO2 , 5.24-73.71 × 10-3 M-1 s-1 . The phenyl substituted adduct regioselectively elicits 52% of benzoic acid as the major product...
February 28, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Xuan Huang, Li Chen, You-Bing Xia, Min Xie, Qin Sun, Bing Yao
AIMS: Electroacupuncture (EA) is an effective and safe therapeutic method widely used for treating clinical diseases. Previously, we found that EA could decrease serum hormones and reduce ovarian size in ovarian hyperstimulation syndrome (OHSS) rat model. Nevertheless, the mechanisms that contribute to these improvements remain unclear. MATERIALS AND METHODS: HE staining was used to count the number of corpora lutea (CL) and follicles. Immunohistochemical and ELISA were applied to examine luteal functional and structural regression...
March 15, 2018: Life Sciences
N J Lee, I M Clarke, R F Enriquez, V Nagy, J Penninger, P A Baldock, H Herzog
RANKL signalling known to be important for the control of bone mass, has recently also been implicated in the brain to control thermoregulation, however, it is not known which neuronal pathways are involved and whether other aspects of energy homeostasis are also affected. Here we show that selective deletion of RANK from NPY neurons down-regulated NPY mRNA expression in the hypothalamus. While comprehensive phenotyping of germline-induced NPY neuron specific RANK deficient mice revealed no significant changes in physical or metabolic parameters, adult onset deletion of RANK from NPY neurons led to a significant increase in fat mass and a decrease in whole body bone mineral content and bone mineral density...
February 15, 2018: Neuropeptides
Alieke Reijnen, Elbert Geuze, Iris Eekhout, Adam X Maihofer, Caroline M Nievergelt, Dewleen G Baker, Eric Vermetten
In order to decrease the risk of developing stress-related disorders after military deployment, biological vulnerability factors should be identified. Neuropeptide Y (NPY) is a peptide neurotransmitter that is associated with modulation of the stress response. Using the data of two longitudinal prospective cohort studies (N = 892 and N = 2427), plasma NPY (pNPY) was assessed as a possible susceptibility biomarker for the development of PTSD symptoms over time. Data collection started prior to deployment and follow-up assessments were completed up to two years after deployment...
February 19, 2018: Biological Psychology
Thomas A Lutz, Bernd Coester, Lynda Whiting, Ambrose A Dunn-Meynell, Christina N Boyle, Sebastien G Bouret, Barry E Levin, Christelle Le Foll
Amylin phosphorylates ERK (p-ERK) in the area postrema (AP) to reduce eating and synergizes with leptin to phosphorylate STAT3 in the arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei, to reduce food intake and body weight. The current studies assessed potential amylin and amylin-leptin ARC/VMN interactions on ERK signaling and their roles in postnatal hypothalamic pathway development. In amylin knockout (KO) mice, the density of agouti-related protein (AgRP) immunoreactive (IR) fibers in the hypothalamic paraventricular nucleus (PVN) was increased, while the density of α-melanocyte stimulating hormone (αMSH) fibers was decreased...
February 21, 2018: Diabetes
M Szlis, J Polkowska, E Skrzeczyńska, B J Przybył, A Wójcik-Gładysz
The participation of peripheral peptides in the processes regulating the food intake (energy homeostasis) at the central nervous system level remains unclear. This study focuses on the role of obestatin in neuronal activity within the hypothalamic appetite-regulating network in ruminants. The animals (n = 28) were randomly divided into two groups. The sheep in the control group received intracerebroventricular infusions of the Ringer-Locke solution, and the sheep in obestatin group were infused with obestatin (diluted in the Ringer-Locke solution) at 25 μg per 120 μl/hr...
February 21, 2018: Journal of Animal Physiology and Animal Nutrition
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