Dissertation > Excellent graduate degree dissertation topics show

Mechanism of Hyperghrelinemia in Snord116Knockout Mouse Model of Prader-Willi Syndrome

Author: LinDaHe
Tutor: JinQuanWen;DingFeng
School: Xiamen University
Course: Cell Biology
Keywords: PWS Snord116knockout mice Ghrelin autonomic nervous system
CLC: R589.2
Type: PhD thesis
Year: 2012
Downloads: 3
Quote: 0
Read: Download Dissertation

Abstract


Prader-Willi syndrome (PWS) is a complex human hereditary disease of obesity. It is caused by the lack of expression of paternally imprinted genes from chromosome15q11-ql3. Latest reports confirmed that Snord116is the most critical gene for PWS, whose most prominent features includes over-eating (hyperphagia), obesity and2-3fold elevated blood ghrelin levels (hyperghrelinemia). The etiology for PWS symptoms is unknown. This article aims to take advantage of a mouse model of PWS, Snord116knockout mice to explore the mechanism of hyperphagia and hyperghrelinemia in PWS.Firstly, because ghrelin can promote gastric motility, we hypothesized that the hyperphagia in Snord116knockout mice may be due to fast gastric emptying. We found, however, that the gastric emptying rate of the knockout mice was significantly lower than that of the wild-type mice, indicating that hyperphagia is not caused by a higher gastric emptying rate. Secondly, blood ghrelin is secreted mainly from stomach, so we detect the distribution of the ghrelin cells and Snord116in stomach. We found that ghrelin cells are located in the lower portion of the gastric mucosa layer, and Snord116distributed only between the stomach wall circular and longitudinal muscle layers and with no co-localization with ghrelin cells, which indicated that Snord116can not affect ghrelin cells directly. Thirdly, we tested the levels of gastric ghrelin mRNA and peptide, and found no significant difference of ghrelin mRNA levels between WT and knockout mice, but the levels of whole stomach ghrelin peptide were significantly lower in Snord116knockout mice. This implied that the hyperghrelinemia of knockout mice may not be due to the excessive synthesis of ghrelin protein, but due to excessive secretion.There were two ways that could cause excessive ghrelin secretion in knockout mice. Firstly, gastric ghrelin cells may be overly sensitive to normal extracellular stimulatory signals. Secondly, there could be an abnormally strong stimulatory secretive signal. To distinguish the two scenarios, we measured ghrelin secretion in response to stimulatory signals. We injected muscarinic receptor agonist, α-adrenergic receptor antagonist, and β-adrenergic receptor agonist, and found that serum ghrelin levels were increased by all3chemicals to similar extents for Snord116knockout mice and WT mice. This study demonstrated that the secretion of ghrelin cells is normally modulated by the neurotransmitters of the autonomic nervous system in the knockout mice. Hence, the hyperghrelinemia in Snord116knockout mice is unlikely to be a defect in the secretory response to stimulation signal, but rather, it is likely that higher stimulatory signal was present in Snord16knockout mice.

Related Dissertations

  1. The Changes of Serum Levels of Ghrelin and IGF-1 in Idiopathic Short Stature Children and Their Relationship with Helicobacter Pylori Infection,R723
  2. Hypothalamus - the hippocampus Ghrelin neurons projected and hippocampal microinjection Ghrelin rats feeding , body weight and gastric motility,R363
  3. Analyze of Ambulatory Blood Pressure with Vasovagal Syncope in Children and Adolescents,R725.4
  4. Clinical studies of perioperative autonomic nerve function monitoring methods and control,R614
  5. Migraine patients 24-hour ambulatory blood pressure variability,R747.2
  6. A Study Implementation of Precaution Strategies Against PWS Trojan Attack,TP393.08
  7. Histological Observation and Expression of Interrelated Polypeptides in Gastrointestinal Tract and Liver of Buteo Hemilasius and Asio Otus,Q954
  8. The Correlation between Serum Ghrelin Levels and Body Composition in Premenopausal Women with Different Thyroid Functional Status,R581
  9. The Distribution of Oxytocin and Ghrelin in the Hypothalamus of Mice and Its Relationship with Obesity,Q41
  10. Age-Related Expression of Ghrelin and IFN-γ in Small Intestine of Ostrich,S852.4
  11. The Clinical Study of the Efficacy and Its Impact Factors in Radionuclide 32P Treatment of Cutaneous Hemangioma,R739.5
  12. Ghrelin antral smooth muscle contraction , [ Ca ~~ ( 2 ) ] _i and IK_ (( Ca ) ) channel open with NO,R333
  13. Clinical Analysis of Cardiac Arrhythmia in Patients with Obstructive Sleep Apnea-hypopnea Syndrome,R766
  14. Effects of Ghrelin on Cognitive Function in Diabetic Rats and Its Machnism,R965
  15. The Clinical and Experimental Study of Shu Gan He Wei Jiang Ni Decoction on Gastroesophageal Reflux Disease,R259
  16. Clinical Significance of Ghrelin and Inflammatory Cytokines Detected in the Peripheral Blood of Patients with Chronic Hepatic Disease,R446.6
  17. Ghrelin effects and mechanism of guinea pig gastric smooth muscle contraction and relaxation activities,Q4
  18. Ghrelin and Obestatin , on spatial learning and memory abilities of,R33
  19. Ghrelin inhibition of colonic epithelial cell apoptosis and its signaling pathway,R574
  20. Sleep disorders in patients with functional dyspepsia gastric motor function in,R740
  21. Detection of Plasma Levels of Ghrelin, Leptin, Insulin and Proinsulin in Patients with Pancreatic Endocrine Tumors and Expression of Ghrelin and GHS-R 1A in Tumor Tissues,R735.9

CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Metabolic diseases > Lipodystrophy
© 2012 www.DissertationTopic.Net  Mobile