Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The effects of early life trauma on the neurochemistry and behaviour of the adult rat
Thesis (PhD (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Stellenbosch : University of Stellenbosch
2008
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613788462645248 |
|---|---|
| access_status_str | Open Access |
| author | Uys, Joachim De Klerk |
| author2 | Daniels, M. W. U. |
| author_browse | Daniels, M. W. U. Uys, Joachim De Klerk |
| author_facet | Daniels, M. W. U. Uys, Joachim De Klerk |
| author_sort | Uys, Joachim De Klerk |
| collection | Thesis |
| dc_rights_str_mv | University of Stellenbosch |
| description | Thesis (PhD (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/1234 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:41:42.984Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2008 |
| publishDateRange | 2008 |
| publishDateSort | 2008 |
| publisher | Stellenbosch : University of Stellenbosch |
| publisherStr | Stellenbosch : University of Stellenbosch |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/1234 The effects of early life trauma on the neurochemistry and behaviour of the adult rat Uys, Joachim De Klerk Daniels, M. W. U. Stein, D. J. University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Medical Physiology. Theses -- Medical physiology Dissertations -- Medical physiology Hippocampus (Brain) Psychic trauma Stress (Psychology) Anxiety Glucocorticoids -- Receptors Rats as laboratory animals Rats -- Effect of stress on Neurochemistry Medicine Thesis (PhD (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006. Early life trauma leads to behavioural abnormalities later in life. These include mood and anxiety disorders such as depression and posttraumatic stress disorder (PTSD). This association may be due in part to the effects of trauma on brain development. Data from basic and clinical experiments suggest that alterations in the hippocampus may be fundamental to the development of these disorders. Here we used an animal model of early life trauma to investigate its effects on the behaviour and neurochemistry of the adult rat. Adolescent rats were subjected to time-dependent sensitization stress consisting of a triple stressor (2 hours restraint, 20 min swim stress and exposure to ether vapour) on post-natal day (PND) 28, a single re-stress on PND 35 (20 min swim stress), and a second re-stress in adulthood (PND 60, 20 min swim stress). The rationale was that the frequency of exposure to situational reminders contributes to the maintenance over time of fear-related behavioural disturbances. The effects of trauma on the hypothalamus-pituitary-adrenal-axis, hippocampal and plasma neurotrophin levels, behaviour and phosphoinositide-3 kinase (PI-3 kinase) signaling proteins were initially investigated. In addition, proteomic technologies such as protein arrays and 2D-SDS PAGE combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) were employed to study trauma-induced effects on the hippocampus. Traumatized animals showed a decrease in glucocorticoid receptors in the dentate gyrus of the hippocampus and an increase in basal corticosterone levels 24 hours after adulthood re-stress. These effects were reversed by pretreatment with the serotonin selective reuptake inhibitor, escitalopram. A decrease in the neurotrophins, BDNF and NT-3 were evident 8 days, but not 24 hours after adulthood re-stress. This decrease was not accompanied by decreases in plasma neurotrophin or PI-3 kinase, protein kinase B (PKB), phosphatase and tensin homologue (PTEN), phospho-forkhead and phospho-AFX protein levels. In addition, traumatized animals showed increased rearing in both the elevated plus maze and open field. Proteomic analysis of trauma-induced changes in the hippocampus show increases in Ca2+ homeostasis / signaling proteins such as S-100B, phospho-JNK and calcineurin. Apoptotic initiator proteins, including caspase 9, -10 and -12 were increased and there was evidence of cytoskeletal protein dysregulation. Furthermore, cell cycle regulators and energy metabolism proteins were decreased. These effects indicate to a cellular state of cell cycle arrest after increased calcium influx to avoid apoptosis. Our data suggest that adolescent trauma with adulthood re-stress may affect numerous systems at different levels. These include neuroendocrine-, protein systems and behaviour, and confirmed that a systems biology approach is needed for a better understanding of the neurobiology of mental disorders. Doctoral 2008-08-04T12:39:09Z 2010-06-01T08:16:05Z 2008-08-04T12:39:09Z 2010-06-01T08:16:05Z 2006-12 Thesis http://hdl.handle.net/10019.1/1234 en University of Stellenbosch application/pdf Stellenbosch : University of Stellenbosch |
| spellingShingle | Theses -- Medical physiology Dissertations -- Medical physiology Hippocampus (Brain) Psychic trauma Stress (Psychology) Anxiety Glucocorticoids -- Receptors Rats as laboratory animals Rats -- Effect of stress on Neurochemistry Medicine Uys, Joachim De Klerk The effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| title | The effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| title_full | The effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| title_fullStr | The effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| title_full_unstemmed | The effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| title_short | The effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| title_sort | effects of early life trauma on the neurochemistry and behaviour of the adult rat |
| topic | Theses -- Medical physiology Dissertations -- Medical physiology Hippocampus (Brain) Psychic trauma Stress (Psychology) Anxiety Glucocorticoids -- Receptors Rats as laboratory animals Rats -- Effect of stress on Neurochemistry Medicine |
| url | http://hdl.handle.net/10019.1/1234 |
| work_keys_str_mv | AT uysjoachimdeklerk theeffectsofearlylifetraumaontheneurochemistryandbehaviouroftheadultrat AT uysjoachimdeklerk effectsofearlylifetraumaontheneurochemistryandbehaviouroftheadultrat |