Cumulative modeling of Maternal Immune Activation to assess risk factors of common neurodevelopmental disease

Summary

Neurodevelopmental disorders such as epilepsy, autism, Tourette syndrome or ADHD affect 10% of children. There is increasing evidence that maternal inflammation whilst pregnant, termed maternal immune activation (MIA), increases the frequency of neurodevelopmental and associated mental health disorders. Common pro-inflammatory states such as obesity, stress, depression, poor diet, psychosocial challenges, asthma, autoimmunity and infection in the mother have all been implicated in contributing to these diseases in the offspring. This study will, for the first time, explore how cumulative exposure to pro-inflammatory states results in increased fetal neuroinflammation and increased severity of neurodevelopmental problems using a novel mouse model.

Supervisor(s)

Dr Markus Hofer

Research Location

School of Life and Environmental Sciences

Program Type

Masters/PHD

Synopsis

Neurodevelopmental disorders such as epilepsy, autism, Tourette syndrome or ADHD affect 10% of children. These diseases a huge burden on families and society and their prevalence is growing. There is increasing epidemiological and animal model evidence to show that maternal inflammation whilst pregnant, termed maternal immune activation (MIA), causes fetal brain inflammation increasing the frequency of neurodevelopmental and associated mental health disorders. Common pro-inflammatory states such as obesity, stress, depression, poor diet, psychosocial challenges, asthma, autoimmunity and infection in the mother have all been implicated in contributing to these diseases in the offspring. The precise mechanisms of how inflammation in the mother results in inflammation and long-term developmental changes in the fetal brain are yet to be fully identified. This study will, for the first time, explore how cumulative exposure to pro-inflammatory states results in increased fetal neuroinflammation and increased severity of neurodevelopmental problems. For this, we will develop a novel mouse model. In addition, using our mouse model, we will specifically explore how the placenta responds to maternal inflammation at the maternal and fetal interface, and how inflammation in the fetus affects the neurovascular unit of the blood brain barrier and secondary microglia activation. This proposal will pursue innate immune signaling across the maternal-placenta-fetal brain axis, with specific focus on toll-like receptor signaling (TLR), interferon signaling and complement activation.

Additional Information

HDR Inherent Requirements

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

- Confidential disclosure and registration of a disability that may hinder your performance in your degree;
- Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
- Ability to perform independently and/or with minimal supervision;
- Ability to undertake certain physical tasks (e.g. heavy lifting);
- Ability to undertake observatory, sensory and communication tasks;
- Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
- Ability to work in confined spaces or at heights;
- Ability to operate heavy machinery (e.g. farming equipment);
- Hold or acquire an Australian driver’s licence;
- Hold a current scuba diving license;
- Hold a current Working with Children Check;
- Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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Keywords

Maternal immune activation; neurodevelopment; CNS; neuroinflammation; interferon; mouse model; risk factors; MIA; blood brain barrier; autism; fetal; brain development

Opportunity ID

The opportunity ID for this research opportunity is: 2816

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