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

Dev Neurosci. 2022;44(6):547-556. doi: 10.1159/000525821. Epub 2022 Jul 7.

Abstract

The purpose of this study was to examine whether the Cronobacter sakazakii 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/Escherichia coli OP50/C. sakazakii 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 C. sakazakii infection causes a deficit in recognition of novel objects from known objects. Further, our analysis showed that C. sakazakii 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.

Keywords: BDNF; Cronobacter sakazakii; Novel object recognition; PSD-95; Reelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cronobacter sakazakii* / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Inflammation
  • Memory Disorders
  • Meningitis*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Serine Endopeptidases / metabolism
  • Signal Transduction

Substances

  • Extracellular Matrix Proteins
  • Cell Adhesion Molecules, Neuronal
  • Serine Endopeptidases
  • Receptors, N-Methyl-D-Aspartate