Dissertation > Excellent graduate degree dissertation topics show

Functional Study of Schizophrenia Susceptibility Gene DTNBP1in Drosophila

Author: ShaoLiSha
Tutor: ZhongYi
School: Tsinghua University
Course: Biology
Keywords: dysbindin schizophrenia Drosophila disease model dopamine glia
CLC: R749.3
Type: PhD thesis
Year: 2011
Downloads: 53
Quote: 0
Read: Download Dissertation

Abstract


The imbalance of multiple neurotransmitter systems is a strikingpathophysiological feature of many mental disorders, schizophrenia in particular. Ithas been a challenge in delineating underlying mechanisms of how the geneticsusceptibility of schizophrenia confers to its pathophysiological and clinicalmanifestations.In the current study, we began our inquiry from the analysis of a Drosophilamutant, dysb1, in the homolog of schizophrenia susceptibility gene DTNBP1(Ddysb). We found that the reduced expression of Ddysb in dysb1mutant lead toboth defected glutamatergic transmission and elevated dopamine level as well as aserial of behavioral abnormalities including memory deficits, hyperactivity, andmating disorientation. Although widely distributed in Drosophila brain, onlyDdysb’s function in neurons is related to the glutamatergic transmission and memoryperformance, and only its function in glial cells plays a role in regulating theindividual development, brain dopamine level, locomotor activity, and matingorientation. This observation suggests the independent functions of Ddysb inneurons versus glia. Further pharmacological and genetic evidence revealed that thehypoglutamatergia in dysb1mutant is responsible for its memory impairment, andthe hyperdopaminergia leads to abnormal locomotion and altered mating orientation.In search of how Ddysb regulates dopamine level in glial cells, we found that aglia-specific N-β-alanyl-biogenic amine synthetase, ebony, is decreasedsignificantly in both the mRNA and the protein level. A positive correlation betweenthe expression of Ddysb and Ebony was also disclosed in further studies. Thus,Ddysb regulates glutamatergic transmission through its neuronal function anddopamine metabolism through regulation of Ebony expression in glial cells.Although Ddysb is essential for the individual development, acute induction ofDdysb transgene rescued the phenotypes in the dysb1mutant, suggesting that Ddysbplays an acute physiological role in regulating neurotransmitters and behaviors. Inaddition, all the phenotypes in dysb1mutant were rescued by expression of humanDTNBP1transgene, indicating that there exists substantial conservation between human DTNBP1and Ddysb. Furthermore, our preliminary data showed that Ddysbinteracted with another schizophrenia susceptibility gene DISC1on the participationof glutamatergic transmission and reversal learning, which expands our research onthe genetic network of Ddysb.

Related Dissertations

  1. Study on Association of Borna Disease Virus Infection with Encephalitis and Schizophrenia,R512.3
  2. The Roles of Spinal Cord Glia in Bee Venom-induced Nociception and Inflammation in Concious Rats,R741
  3. An Analysis of Serum Levels of Brain-derived Neurotrophic Factor and the Related Factors in Uygur and Han Patients with Schizophrenia in Xinjiang,R749.3
  4. A Volumetric Study of External Capsule, Extreme Capsule and Inferior Frontal Gyrus White Matter in First-Episode Paranoid Schizophrenia,R749.3
  5. Research on the Relationship between Negative Symptoms and Serum Testosterone Concetration in Male Chronic Schizophrenia Patients,R749.3
  6. Four kinds of atypical antipsychotics in patients with schizophrenia serum prolactin and Blood Lipid,R749.3
  7. Schizophrenia cognitive function and quality of life research,R749.3
  8. Effects of Ketamine on Proliferation and Apoptosis of Pheochromocytoma Cell,R736.6
  9. A Study of VTA’s Plasticity and Dopamine Neurons Membrane Current Mediated by NMDA Receptor in the VTA on Heroin-addicted Rats,R749.6
  10. Borna Disease Virus P40gene Fragments Detected in Blood of Patients with Viralencephalitis and Schizophrenia,R749.3
  11. Effects of Antipsychotics Treatment on Blood-Lipid of Patients with Schizophrenia,R749.3
  12. Effects of Risperidone and Aripiparzole on Glucose, Lipid and Plasma Cytokine Levels in Schizophrenic Patients,R749.3
  13. Research on Preparation of Dopamine Composite Films on Stainlees Steel and Corrosion Resistance,TG174.44
  14. Effects of Antipsychotics Treatment on Blood Glucose of Patients with Schizophrenia,R749.3
  15. Electrophysiological and Behavioral Studies of Dopamine D1 Receptors in Rat Globus Pallidus,R742.5
  16. Interaction on the Amygdala Activation Between Personal Familiarity and Fear Expression in Face Perception: An fMRI Study,R445.2
  17. A Study of Schizophrenia Model by Chronic and Acute NMDAR Antagonist MK-801 Exposure in Perinatal and Adult Rats,R749.3
  18. Evaluating Effectiveness of Psychosocial Rehabilitation on Patients with First-episode of Schizophrenia,R749.3
  19. Three Cases of Schizophrenia,R749.3
  20. Efficacy and Compliance of Schizophrenia by Drug Self-management Skills Combined Family Intervention Treatment,R749.3
  21. To Investigate Some Event-Related Potentials in Schizophrenia,R749.3

CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Schizophrenia
© 2012 www.DissertationTopic.Net  Mobile