Reduced Reelin Expression Induces Memory Deficits through Dab-1/ NMDAR Signaling Pathway: <b><i>Cronobacter sakazakii</i></b> Infection in a Rat Model of Experimental Meningitis

Abstract

The purpose of this study was to examine whether the <i>Cronobacter sakazakii</i> infection-induced inflammation alters the Reelin signaling pathway that is involved in learning and memory. To test this, postnatal day (PND)-15 rat pups were either treated with Luria Bertani broth/<i>Escherichia coli</i> OP50/<i>C. sakazakii</i> through oral gavage or maintained as control and allowed to stay with their mothers until PND-24. Experimental groups’ rats were subjected to long-term novel object recognition test during their adolescent age PND-30–32. Observed behavioral data showed that <i>C. sakazakii</i> infection causes a deficit in recognition of novel objects from known objects. Further, our analysis showed that <i>C. sakazakii</i> infection-mediated inflammation decreases the Reelin expression by proteolytic cleavage and alters its receptor apolipoprotein E-receptor (ApoER)-2 splice variants ApoER2 (ex19) and ApoER2 (Δ). Subsequently, downregulated Reelin alters the phosphorylation of disabled adapter protein (Dab)-1 and leads to differential expression of N-methyl-D-aspartate (NMDA) receptor subunits 2A and 2B. Further, the NMDA receptor influences the expression of postsynaptic density (PSD)-95 protein and brain-derived neurotrophic factor (BDNF). Observed results suggest a deficit in recognition of novel objects possibly due to the alternation in Reelin signaling pathway.