Profiling metabolome of mouse embryonic cerebrospinal fluid following maternal immune activation.

ABSTRACT

The embryonic cerebrospinal fluid (eCSF) plays an essential role in the development of the central nervous system (CNS), influencing processes from neurogenesis to lifelong cognitive functions. An important process affecting eCSF composition is inflammation. Inflammation during development can be studied using the maternal immune activation (MIA) mouse model, which displays altered cytokine eCSF composition and mimics neurodevelopmental disorders including autism spectrum disorder (ASD). The limited nature of eCSF as a biosample restricts its research and has hindered our understanding of the eCSF's role in brain pathologies. Specifically, investigation of the small molecule composition of the eCSF is lacking, leaving this aspect of eCSF composition under-studied. We report here the eCSF metabolome as a resource for investigating developmental neuropathologies from a metabolic perspective. Our reference metabolome includes comprehensive MS1 and MS2 datasets and evaluates two mouse strains (CD-1 and C57Bl/6) and two developmental time points (E12.5 and E14.5). We illustrate the reference metabolome's utility by using untargeted metabolomics to identify eCSF-specific compositional changes following MIA. We uncover MIA-relevant metabolic pathways as differentially abundant in eCSF and validate changes in glucocorticoid and kynurenine pathways through targeted metabolomics. Our resource can guide future studies into the causes of MIA neuropathology and the impact of eCSF composition on brain development.