Glucocorticoid signature in a neuronal genomic context

Leiden Repository

Glucocorticoid signature in a neuronal genomic context

Type: Doctoral Thesis
Title: Glucocorticoid signature in a neuronal genomic context
Author: Polman, J.A.E.
Issue Date: 2016-05-10
Keywords: Glucocorticoid receptor
Hippocampus
mTOR
HPA-axis
Cortisol
ChIP-sequencing
Stress
Abstract: During this research we wanted to gain more insight into the potential gene repertoire that is involved in the hippocampus when coping with stress and regulating learning and memory processes. To investigate this further we aimed to answer the question:""What are the primary genomic binding sites of the by stress and thus cortisol stimulated protein receptors MR and GR in the hippocampus?" To answer this question, new methods have been applied to determine where exactly MR and GR bind to the DNA, to find out which genes are potentially involved during stress management. As a result we have identified thousands of GR-binding sites at the DNA of which we have analyzed a selection in further detail. One of the identified pathways that have been found to be sensitive for activated GR and corticosteroids is the mTOR pathway. This pathway is involved in neuronal plasticity, which is the fundament for resilience. We have found that expression of the mTOR protein is decreased after exposure to acute stress when the organism has a history of chronic stress. Our results indicate that the reduced resilience after experiencing chronic stress is likely to be mediated by mTOR.
Promotor: Supervisor: E.R. de Kloet Co-Supervisor: N.A. Datson
Faculty: LUMC
University: Leiden
Uri: urn:isbn:9789462993266
Sponsor: The Netherlands Organization for Scientific Research (NWO), Top Institute (TI) Pharma, Human Frontiers of Science Program (HFSP) Royal Netherlands Academy of Arts and Sciences (KNAW).
Handle: http://hdl.handle.net/1887/39295
 

Files in this item

Description Size View
application/pdf Cover 359.3Kb View/Open
application/pdf Full text 5.311Mb View/Open
application/pdf Title page_List of abbreviations_Contents 140.8Kb View/Open
application/pdf Chapter 1 General introduction 1.213Mb View/Open
application/pdf Chapter 2 1.605Mb View/Open Full text at publisher site
application/pdf Chapter 3 942.0Kb View/Open Full text at publisher site
application/pdf Chapter 4 1.043Mb View/Open Full text at publisher site
application/pdf Chapter 5 649.8Kb View/Open Full text at publisher site
application/pdf Chapter 6 General discussion 458.8Kb View/Open
application/pdf Chapter 7 Summary 151.5Kb View/Open
application/pdf Chapter 8 Summary in Dutch 148.5Kb View/Open
application/pdf References 195.0Kb View/Open
application/pdf Curriculum Vitae_Publication list 113.8Kb View/Open
application/pdf Propositions 481.7Kb View/Open

This item appears in the following Collection(s)