Microglia in the embryonic neocortex - the effect of maternal inflammation

Abstract

Infection during pregnancy can lead to maternal inflammation. Several studies have suggested that maternal inflammation increases the risk on neuropsychiatric disorders, like autism, in the offspring. The cause of autism remains unknown, it is thought to be a complex interaction of different factors. A study of Vargas et al demonstrated the presence of an active neuroinflammatory process in the brains of autistic patients, with marked microglial cell activation. Microglia colonize the central nervous system early in embryonic development, at the moment that neuronal migration to the cortical plate is peaking and neuronal differentiation and synaptogenesis are underway. By their production of growth factors, it has been suggested that microglia can influence axonal growth and synaptogenesis. Based on these findings, we aim at studying the localization and activation stages of the microglia present in the embryonic murine neocortex in healthy embryos subjected to maternal inflammation. Transgenic CX3CR1 + /eGFP embryos were isolated at the desired age. Heads were fixed in paraformaldehyde, cryoprotected with sucrose and frozen in optimal Cutting Temperature compound. Coronal sections were stained for Iba-1, CD68, CD11b and MHC II.

At E13.5, few microglia are present in the embryonic cortex (5,2 × 10-5 ± 3,7 × 10−6 cells/μm2, n = 6). Their number has increased at E14.5 (8.1 × 10−5 ± 2.9 × 10−6 cells/μm2, n = 6). Most microglia reside at the meninges and some are present in the ventricle. They have a round morphology, with one or two ramifications. Although their morphology resembles that of (early) activated microglia, their expression profile suggests that they are 'resting cells'. The ramifications could indicate that the microglia migrate along radial glia. We expect to find more cells, in a higher activation stage, in embryos subjected to maternal inflammation.