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Metabolomics of Mouse Embryonic CSF Following Maternal Immune Activation

Petrova, B.; Lacey, T. E.; Culhane, A. J.; Cui, J.; Raskin, A.; Mishra, A.; Lehtinen, M. K.; Kanarek, N.

2023-12-08 neuroscience
10.1101/2023.12.06.570507 bioRxiv
Show abstract

The cerebrospinal fluid (CSF) serves various roles in the developing central nervous system (CNS), from neurogenesis to lifelong cognitive functions. Changes in CSF composition due to inflammation can impact brain function. We recently identified an abnormal cytokine signature in embryonic CSF (eCSF) following maternal immune activation (MIA), a mouse model of autism spectrum disorder (ASD). We hypothesized that MIA leads to other alterations in eCSF composition and employed untargeted metabolomics to profile changes in the eCSF metabolome in mice after inducing MIA with polyI:C. We report these data here as a resource, include a comprehensive MS1 and MS2 reference dataset, and present additional datasets comparing two mouse strains (CD-1 and C57Bl/6) and two developmental time points (E12.5 and E14.5). Targeted metabolomics further validated changes upon MIA. We show a significant elevation of glucocorticoids and kynurenine pathway related metabolites. Both pathways are relevant for suppressing inflammation or could be informative as disease biomarkers. Our resource should inform future mechanistic studies regarding the etiology of MIA neuropathology and roles and contributions of eCSF metabolites to brain development.

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