- Title
- The effects of maternal stress on perinatal neurodevelopment and behaviour
- Creator
- Bennett, Greer
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2015
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Maternal stress is associated with persistent changes in the development of offspring, which are thought to be ‘programmed’ in utero. Alterations in the brain development of prenatally stressed offspring has been linked with increased risks for behavioural and cognitive abnormalities later in life. There is evidence to suggest that the time at which a mother experiences stress during pregnancy may be critical in determining the specific outcomes in her offspring due to the effects on fetal ontogenesis at different times in gestation. Neurosteroids including the progesterone metabolite, allopregnanolone, have been found to act as endogenous neuroprotective agents in the fetal brain during times of stress and pregnancy compromise. Due to a high placental secretion of progesterone throughout pregnancy, allopregnanolone levels are elevated in both the mother and the fetus. Allopregnanolone has important trophic actions through binding to the GABAA inhibitory receptor and is essential for normal neurodevelopment. Therefore, the aims of the studies described in this thesis were to assess the effects of maternal stress at different times in gestation on perinatal brain development and behavioural outcomes at juvenility and also to determine the role of allopregnanolone and the neurosteroid system in modulating the effects of stress on the perinatal brain. The effect of prenatal maternal stress during pregnancy was assessed using an established guinea pig model. Pregnant dams were subjected to strobe light exposure to induce stress beginning from ‘early’ (0.5 gestation), ‘mid’ (0.7 gestation) or ‘late’ (0.8 gestation) pregnancy. Effects of prenatal stress were examined in the hippocampus, subcortical white matter and cerebellum of offspring as these regions are known to be vulnerable to the effects of stress and are also implicated in many of the behavioural outcomes observed in offspring. Assessments of perinatal brain development were used primarily with immunohistochemical markers for mature myelinating oligodendrocytes and reactive astrocytes, which assess two key cell populations in the brain. Fetal tissues were collected at term (approximately 69 days gestation). In offspring that were delivered, behavioural testing was performed at the equivalent of childhood/juvenility (18 days postnatal age), which is an important time in postnatal development when many altered behaviours become apparent. Maternal and offspring cortisol concentrations were measured at the time of prenatal stress exposure and postnatal behavioural testing respectively. Brain and plasma allopregnanolone were measured along with neurosteroidogenic enzymes and key GABAA receptor subunits to assess the role of the neurosteroid system in these offspring. The major findings of the present studies were that maternal stress may lead to the development of marked changes in behaviour in juvenile offspring. Specifically, prenatally stressed offspring showed increased anxiety and neophobia at juvenility. These changes in behaviour were associated with reductions in markers for myelination and reactive astrocyte expression, primarily in the CA1 region of the hippocampus. In some brain regions, there were sexually dimorphic outcomes between male and female brain development however both sexes showed increased anxious behaviour and neophobic responses in juvenility, irrespective of the timing of maternal stress exposure. These studies further showed that offspring exposed to prenatal stress beginning earlier in gestation also showed sustained reductions in circulating allopregnanolone levels after birth, which suggests that the neurosteroid system may be altered by early stress exposure in utero and these changes may contribute to adverse behavioural outcomes in offspring. These studies have demonstrated the marked effects of maternal stress on perinatal brain development that may contribute to the altered behavioural phenotypes observed in later life. Additionally, this work further indicates there may be an important role for reduced allopregnanolone signalling in the development of these prenatally stressed offspring. The field of developmental origins of health and disease (DOHaD) is a rapidly growing one, and maternal stress is certainly an important factor for the programming of outcomes in offspring with the current studies suggesting that preventive approaches such as those that modulate neurosteroid processes warrant further attention.
- Subject
- stress; prenatal Stress; programming; thesis by publication; neurosteroids; allopregnanolone; brain development; neurodevelopment; anxiety; fear; neophobia; behaviour
- Identifier
- http://hdl.handle.net/1959.13/1310072
- Identifier
- uon:21983
- Rights
- Copyright 2015 Greer Bennett
- Language
- eng
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Abstract | 188 KB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Chapters 1-3 | 11 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT03 | Chapters 4-7 | 17 MB | Adobe Acrobat PDF | View Details Download |