Cronobacter sakazakii Infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-κβ and ASK1 Pathways

• Published in: Journal of molecular neuroscience 2021, Vol.71 (1), p.28-41
• Main Authors: Vinay, Ponnusamy, Karen, Christopher, Balamurugan, Krishnaswamy, Rajan, Koilmani Emmanuvel
• Format: Article
• Language: English
• Subjects: ADAM protein; ADAMTS-1 protein; AKT protein; Alternations; Anaphylatoxins; Apoptosis; Associative learning; Associative memory; Biomedical and Life Sciences; Biomedicine; c-Jun protein; Cell Biology; Cognitive tasks; Complement; Complement activation; Complement component C5a; Cronobacter sakazakii; E coli; Infections; Inflammation; Interleukin 6; JNK protein; Kinases; Learning; Lymphocytes B; MAP kinase; Neurochemistry; Neurology; Neurosciences; NF-κB protein; Proteins; Proteomics; Rodents; Sepsis; Serotonin; Serotonin transporter; Thrombospondin; Transcription factors; α-Interferon
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-020-01622-8

This study was designed to test whether the Cronobacter sakazakii infection-impaired contextual learning and memory are mediated by the activation of the complement system; subsequent activation of inflammatory signals leads to alternations in serotonin transporter (SERT). To test this, rat pups (postnatal day, PND 15) were treated with either C. sakazakii (10 7  CFU) or Escherichia coli OP50 (10 7  CFU) or Luria bertani broth (100 μL) through oral gavage and allowed to stay with their mothers until PND 24. Experimental groups’ rats were allowed to explore (PNDs 31–35) and then trained in contextual learning task (PNDs 36–43). Five days after training, individuals were tested for memory retention (PNDs 49–56). Observed behavioural data showed that C. sakazakii infection impaired contextual-associative learning and memory. Furthermore, our analysis showed that C. sakazakii infection activates complement system complement anaphylatoxin (C5a) (a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1)) and mitogen-activated protein kinase kinase1 (MEKK1). Subsequently, MEKK1 induces pro-inflammatory signals possibly through apoptosis signal-regulating kinase-1 (ASK-1), c-Jun N-terminal kinase (JNK1/3) and protein kinase B gamma (AKT-3). In parallel, activated nuclear factor kappa-light-chain-enhancer B cells (NF-κB) induces interleukin-6 (IL-6) and IFNα-1, which may alter the level of serotonin transporter (SERT). Observed results suggest that impaired contextual learning and memory could be correlated with C5a-mediated NF-κβ and ASK1 pathways.