Maternal immune activation affects precursor cell populations and developmental processes in the rodent spinal cord in a temporally and spatially dependent manner

Abstract

Studies suggest that maternal immune activation (MIA) during pregnancy may be implicated in development of neurological disorders with timing of immune challenge and spatial differences playing an important role. However, further research is necessary in order to elucidate fully the CNS regions, cell populations and timing of gestational vulnerability. As the development of the spinal cord (SC) is well characterised, here we investigate how MIA affects cell populations and developmental processes in this CNS region.Time‐mated dams received an intraperitoneal injection of 100μg/kg lipopolysaccharide (LPS) or saline on embryonic day (E)12 or 16. Embryos were harvested 5hr post‐injection, or delivered and sacrificed at postnatal day (P)14. Offspring were fixed, frozen whole or following SC dissection and cryosectioned. In order to determine how MIA affects oligodendrocyte precursors, microglia, and reelin expression during development, sections were immunostained with Olig2, Iba‐1 and reelin. In addition total RNA was extracted from fresh frozen SCs and prepared for microarray, RNAseq and small RNAseq.At E12, numbers of Olig2+ and Iba‐1+ cells were unchanged 5hrs post‐LPS injection but Olig2+ cells were decreased in the ventral grey matter of the rostral SC at P14. The number of Iba‐1+ cells were unchanged at P14. At E16, Olig2+ and Iba‐1+ cells were decreased in grey and white matter 5 hrs post‐LPS, however by P14 there was no difference between the LPS and saline treated groups. Reelin expression following MIA at E12 appeared unchanged at 5hrs and P14 however, at E16, reelin expression was decreased 5hrs after MIA. Total cell numbers at E16, at both the 5hr and P14 survival times, were unchanged following LPS injection.These findings suggest MIA affects development in the SC in a temporally and spatially precise manner. At E12 MIA does not appear to affect olig2+ oligodendrocyte precursors acutely but may affect their survival to P14. In contrast, at E16, MIA affects Olig2+, Iba‐1+ and reelin expression acutely. Ongoing work is characterising postnatal reelin expression following LPS at E16, and the phenotype of Iba1+ cells to understand more fully the detailed cellular perturbations resulting from MIA.Support or Funding InformationAnatomical Society, Graduate Entry Medical School, Health Research Institute, University of LimerickThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.