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Type: Theses
Title: Neurodevelopmental effects of placental restriction in sheep
Author: Hunter, Damien Seth
Issue Date: 2017
School/Discipline: School of Animal and Veterinary Sciences
Abstract: Intrauterine growth restriction (IUGR) and poor perinatal growth in humans are associated with poorer cognition and memory and altered functional lateralisation. Altered brain morphology and neurodevelopment following IUGR appears responsible, and may be ameliorated by neonatal catch-up growth, however assessing relative effects of prenatal and postnatal growth on cognition in humans is difficult due to environmental confounders. Experimental placental restriction (PR) in sheep, via surgical removal of uterine epithelial attachment sites prior to mating, restricts intrauterine growth and is followed by catch-up growth. Cognitive consequences have not been examined in this model. Effects of sex, age and prior learning on cognition were therefore characterised in control (CON) sheep, then effects of PR on learning, memory, cognition, functional and morphological lateralisation were investigated. Size at birth and neonatal fractional growth rates during the first 16 days of life (ie. neonatal catch-up growth) were measured for CON and PR offspring. Behavioural testing occurred at 18 and 40 weeks old. In maze tasks, trials and time per task, bleats and arm entries were recorded for initial learning (L), memory (M1, M2) and reversal (R1, R2) tasks. Behavioural lateralisation was recorded using obstacle avoidance and maze exit preference tasks, and structural lateralisation were measured in the prefrontal cortex brain region at 52 weeks of age. In CON sheep, naive sheep aged 18 or 40 weeks required longer to complete task R1 than 40 week olds retested after learning the task at 18 weeks old, indicating prior learning was recalled at later ages. The exit route used for earlier learning tasks also predicted speed required to solve task R1 in 40N females. Body weight and skull size at birth did not differ between CON and PR lambs utilised for behavioural testing. At 18 weeks, placentally restricted male lambs took more trials to solve the initial learning task, but required less time to complete task R1 than control males. Trials and time required to solve task M1 in 40 week old males correlated negatively with neonatal growth. Bleat frequency during task R1 in 18 week old females correlated positively with birth weight and neonatal fractional growth rate. In 40 week old females, PR were more strongly lateralised in the maze exit preference task lateralisation than CON. Lateralisation direction was consistent between ages in PR females only, and was more consistent between tasks at 18 weeks in PR than CON females. Behavioural lateralisation did not correlate with perinatal growth, and brain morphology at 52 weeks did not differ between treatments. Correlations between perinatal growth and adult brain morphology were largely limited to males, whereas correlations between behaviour and brain morphology existed largely in females. In conclusion, effects of age, sex and experience on cognitive and behavioural outcomes must be taken into account when evaluating these outcomes in sheep. Effects of PR on cognition and behavioural lateralisation were limited but suggested sex-specific programming of postnatal neurodevelopment. Neonatal growth rate correlated with memory performance in males, suggesting interventions during this period may improve outcomes.
Advisor: Hazel, Susan Jane
Dissertation Note: Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Animal and Veterinary Sciences and Adelaide Medical School, 2017.
Keywords: intrauterine growth restriction
neurodevelopment
sheep
neonatal growth
cognition
learning
memory
lateralization
cerebral asymmetry
Research by Publication
Provenance: Copyright material removed from digital thesis. See print copy in University of Adelaide Library for full text.
This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
DOI: 10.4225/55/5939e1cd1ef86
Appears in Collections:Research Theses

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