Glucocorticoid signature in a neuronal genomic context

Polman, J.A.E. (2016)

Doctoral Thesis

 

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.

 

• Glucocorticoid receptor
• Hippocampus
• mTOR
• HPA-axis
• Cortisol
• ChIP-sequencing
• Stress

• All authors: Polman, J.A.E.
• Supervisor: Kloet, E.R. de
• Co-supervisor: Datson, N.A.
• Committee: Maarel, S.M. van der; Lucassen, P.J.; Martens, G.J.; Meijer, O.C.; Slagboom, P.E.; Vreugdenhil, E.
• Qualification: Doctor (dr.)
• Awarding Institution: LUMC, Leiden University
• Date: 2016-05-10
• ISBN (print): 9789462993266
• Sponsorship: 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).