Current evidence indicates that antenatal corticosteroids (ACS), such as dexamethasone and betamethasone can improve preterm birth outcomes in particular clinical settings [1]. The use of ACS was estimated at 54% among women from 29 low-and middle-income countries (LMICs) [2], and in LMICs there have been concerns of suboptimal clinical practices regarding ACS, including use of low-quality corticosteroids and inadequate assessment of risk for preterm birth, leading to administration of ACS at gestational ages where benefit is controversial [3, 4].
Concerns exist about potential consequences of ACS and hormonal perturbations on prenatal programming of neurodevelopment that may result in long-term neuropathological and neurocognitive sequelae [5]. In this context, the evidence surrounding neurocognitive functioning in children exposed to ACS in LMICs—especially in sub-Saharan Africa, where the burden of preterm birth is highest, is unclear.
This project involves will involve an empirical Developmental Origins of Health and Disease (DOHAD)-preclinical study that will investigate the effects of a clinically relevant dosage of dexamethasone administered to pregnant rats at different time points on long-term neuropathological and neurocognitive sequelae of offspring (viz., establish a neurodevelopmental animal model).
Specifically, effects of dexamethasone treatment on neuroanatomical (e.g., hippocampal and choroid plexus volume), pathological (e.g. synaptic, neuronal and inflammatory markers), epigenetic (e.g., 11β-hydroxysteroid dehydrogenase type 2), and behavioural outcomes (e.g., cognition) will be assessed. Pathological and neurocognitive markers will be probed in offspring at different developmental time-points.
The proposed research topic has important public health implications, especially in bridging knowledge gaps on the seemingly meagre and conflicting evidence regarding long-term impacts of synthetic glucocorticoids on offspring development.
www.b-neuro.com
Eligibility
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC DTP website https://www.bmh.manchester.ac.uk/study/research/mrc-dtp/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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