Maternal Infection Impairs Motor Coordination in an Experimental Meningitis Rat Model Through Altered MMP-2/3/9 Activity, H3K4 Trimethylation, andMethylation.

Abstract

Maternal infection (MI) can increase the risk of neurodevelopmental and behavioural changes. This study examined MI-induced changes in motor coordination through the inflammatory-pathway-mediated epigenetic status of. On gestational day (GD) 10, rats were assigned as (i) Control (Ctrl); (ii)(CS) infection on GD-10 through recto-vaginal colonization; (iii) Negative Control (NC) [infected withand treated with dimethyl sulfoxide (DMSO) 1 h before and 24 h after infection]; and (iv)-infected rats treated with matrix metalloproteinase inhibitor (MMPI), 1 h before and 24 h after infection (CS + MMPI). Offspring were subjected to footprint analysis and the ladder rung walking test, which revealed that MI caused significant deficits in motor coordination. In addition, MI activated complement components-a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1, C5a)-as well as proinflammatory cytokines such as interleukin-6 (IL-6) and matrix metalloproteinases (MMP-2, MMP-3, and MMP-9). Furthermore, the levels of DNA methyltransferase 3 alpha (DNMT3A), methyl-CpG-binding protein 2 (MeCP2), and histone H3 lysine 4 trimethylation (H3K4me3) were elevated in the CS and NC groups. Concurrently, the level ofpromoter methylation increased; as a result, mRNA and protein, as well as postsynaptic density protein-95 (PSD-95), levels were decreased. Overall, the findings suggest that MI altered MMP-2/3/9 activity, H3K4me3, and the methylation of, thereby affecting reelin, synaptic protein expression, and motor coordination in an experimental meningitis rat model.