Investigating the effect of maternal obesity and inflammation on corpus callosum associated microglia during perinatal development

Davis, Jonathan 2023. Investigating the effect of maternal obesity and inflammation on corpus callosum associated microglia during perinatal development. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Microglia have important roles in supporting healthy brain development. Recent research uncovered many microglia populations in the developing brain. There is still much we do not know about developmental microglia. Microglia also form a vital part of the immune system, where they respond to inflammatory stimuli to protect the central nervous system. Inflammatory conditions such as maternal obesity and maternal immune activation are associated with neuropsychiatric and neurodevelopmental disorders, however the mechanisms mediating this relationship are not fully understood. As central nervous system immune cells and important players in neurodevelopment, microglia are at a key position in the relationship between prenatal inflammation and pathological neurodevelopment. Studying the effect of inflammation on developmental microglia therefore provides an opportunity to investigate mechanisms involved in neuropsychiatric or neurodevelopmental disorder. This thesis characterised populations of microglia associated with the developing corpus callosum and investigated the impact of maternal obesity and maternal immune activation on corpus callosum associated microglia and brain development. Microglia form dense clusters in close association with the developing corpus callosum reminiscent of developmental ‘hotspots’. Analysis of expression profiles revealed more diverse microglial populations at the midline than the cortex (Chapter 2). Corpus callosum associated microglia also differed from cortical microglia with regard to birthdate, proliferation rate, ability to migrate and protein expression (Chapter 3). High fat diet models of maternal obesity had variable impacts on offspring development. Corpus callosum organisation and associated microglia differentiation was unaffected by maternal high fat diet (Chapter 4). Models of maternal immune activation also produced variable effects on offspring development but somewhat affected corpus callosum organisation and associated microglia differentiation in addition (Chapter 5). Novel insights into developmental microglia and interactions with maternal inflammation presented in this thesis may provide the basis for further investigations into intervention strategies for neuropsychiatric and neurodevelopmental disorders.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	21 March 2024
Last Modified:	21 Mar 2024 15:47
URI:	https://orca.cardiff.ac.uk/id/eprint/167428

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