Behavioural and developmental consequences of maternal immune activation in offspring
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
One of the fundamental questions in basic disease research is how stressors experienced during critical periods influence the development of adult disease. In particular, stressors experienced during pregnancy have been shown to have effects on the propensity to develop cognitive disorders in offspring. But is this because of a change directly affecting brain development in utero or is it because mothers change their parental behaviour in response to stressors, or a combination? Further, what are the mechanisms underlying such effects? The placenta plays a critical role in maternal-fetal interactions and fetal adaptive responses in utero which may lead to a propensity to disease development later on in life. Prior work has indicated that placental development is affected by maternal stressors, but it remains unclear whether and how this may result in cognitive impairment in offspring.
The proposed project seeks to answer these questions by applying a multidisciplinary approach to map functional changes along a developmental timeline that links placental morphological development to offspring traits, achieved by combining experimental studies in a rodent model system with evaluation of placental morphological development, together with parent-offspring behavioural interactions, cognitive and behavioural analyses. This will be combined with histological investigations and molecular array studies. This will also be complemented by a bioinformatics component to unravel the biological pathways and genetic networks of known candidates for placental function and associated behavioural impairments. The project therefore offers broad scientific training that will cover mammalian disease and behaviour research, histology, physiology, molecular biology, genetics and bioinformatics.
The proposed project seeks to answer these questions by applying a multidisciplinary approach to map functional changes along a developmental timeline that links placental morphological development to offspring traits, achieved by combining experimental studies in a rodent model system with evaluation of placental morphological development, together with parent-offspring behavioural interactions, cognitive and behavioural analyses. This will be combined with histological investigations and molecular array studies. This will also be complemented by a bioinformatics component to unravel the biological pathways and genetic networks of known candidates for placental function and associated behavioural impairments. The project therefore offers broad scientific training that will cover mammalian disease and behaviour research, histology, physiology, molecular biology, genetics and bioinformatics.
Organisations
People |
ORCID iD |
Reinmar Hager (Primary Supervisor) |
Publications
Kowash HM
(2019)
Poly(I:C) source, molecular weight and endotoxin contamination affect dam and prenatal outcomes, implications for models of maternal immune activation.
in Brain, behavior, and immunity
Potter HG
(2019)
Offspring genetic effects on maternal care.
in Frontiers in neuroendocrinology
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M011208/1 | 01/10/2015 | 31/03/2024 | |||
1791568 | Studentship | BB/M011208/1 | 01/10/2016 | 31/03/2021 |
Description | We have optimised a current method for investigating the behavioural changes seen in schizophrenia, allowing a more reliable way to test new therapeutic compounds. We have identified a specific set of cognitive deficits in a rat model of schizophrenia, and are working to identify the mechanisms by which prenatal immune stress causes this through altered neurodevelopment. |
Exploitation Route | This could be used by pharmaceutical companies to test new drugs for schizophrenia. |
Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |