Exposure to a sub-optimal environment during fetal life is known to increase the subsequent risk of developing a range of diseases in adult life, including metabolic and cardiovascular disease. This phenomenon is known as developmental programming. Emergent evidence now suggests that compromise during pregnancy such as stress and/or adverse factors that cause impaired fetal growth, also give rise to broad psychiatric effects and an increased risk of emotional disorders later on in life. The mechanisms however remain unknown, although very recent studies in transgenic mice reveal a role for the placenta in long-term programming of emotional behaviour (in relation to its capacity to meet fetal nutritional requirement).
Despite the now accepted link between restricted calorific intake by the mother during pregnancy and impaired fetal growth as an adverse outcome, one common form of dietary food restriction in humans that has not been studied in detail is the case of Ramadan fasting. Although exempt, many pregnant Muslim women take part in the daily fast during the month of Ramadan. Potential long term effects on the child are not fully known, although an association between exposure to fasting in utero and an increased incidence of mental impairment in children has been shown, and such outcomes may be related to nutrient-modifiable events that occur during in utero during development of the baby.
In order to study the mechanisms that link a sub-optimal maternal diet and cognitive function of the offspring, we have developed a rat model of intermittent fasting during pregnancy, to mimic aspects of Ramadan fasting. Maternal fasting results in the development of lighter placentas and smaller fetuses with reduced length, head and abdominal circumferences. The impaired growth of the brain appears to affect cognitive function and social behaviour: rats whose mother fasted intermittently during pregnancy showed a marked impairment in memory. Furthermore there appears to be a gender-related effect: memory was impaired from 4 weeks of age in females whereas in males memory was comparable with control animals in juveniles but declined with increasing age.
The aim of the proposed project is to determine the effect of maternal intermittent fasting during pregnancy on the development of cognitive function. The first phase of the PhD project will explore behavioural effects and their neurochemical correlates in some detail. The second phase of the PhD project will look at how intermittent fasting during different stages of gestation (early, mid and late) impacts on behavioural affects in the offspring, and whether this relates to expression of neurodevelopmental markers.
Training will be provided in a range of behavioural and cognitive analyses in rodent, as well as molecular and biochemical techniques, including PCR, immunoblotting, immunohistochemistry, enzyme activity and transporter assays. The project will provide in vivo methods training.
Applicants should hold a minimum upper second class honours degree (or equivalent) in a relevant behavioural science, biological/medical science, molecular biology or related discipline. A Masters qualification in a similar area and/or previous research experience would be advantageous.
This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/sponsorship and is due to commence from January 2017 onwards.
Expressions of interest and informal enquires should be directed to Dr Nick Ashton ([email protected]