Antibiotic treatment during post-natal reverses behavioural and molecular alterations in experimental meningitis survivor rat model

Abstract

The present study was aimed to examine the behavioural and molecular alterations in experimental meningitis survivor rat model. On postnatal day (PND)-2, animals were assigned to different groups: (i) Control (Ctrl), (ii) Positive Control [PCtrl: gavaged with Luria-Bertani (LB) broth on PND-2 and received antibiotics treatment (AbT) from PND-5 to 11], (iii) Cronobacter sakazakii (CS: received single dose of live bacterial culture on PND-2) infected. Later, a subset of CS group received antibiotics treatment (AbT) from PND-5 to 11 and assigned as group (iv) (CS + AbT/ survivor). On PND-35, animals were subjected to behavioural tasks [viz., elevated plus maze (EPM) test and step-through inhibitory retention], and sacrificed for molecular analyses. We found that CS infection induces anxiety-like behaviour, impaired short/long-term memory and differentially altered the expression of brain-derived neurotrophic factor (BDNF) splice variants (III, IV and VI), decreased expression of BDNF, Src family tyrosine kinase (FYN), focal adhesion kinase (FAK) and nerve growth factor (NGF). The observed behavioural phenotype and expression pattern of candidate genes fit in the correlation. In addition, NGF expression was reduced in dentate gyrus (DG) and CA1 regions of hippocampus. Notably, antibiotic treatment reduced the anxiety-like behaviour, improved step-through inhibitory retention and suppressed infection induced reduction in BDNF, FYN, FAK and NGF expressions in survivors, however, not comparable to the control group. Overall, our experimental meningitis survivor model demonstrate that antibiotic treatment minimize the C. sakazakii infection induced effect on behaviour and signaling molecules involving in neuronal development, survival, and synaptic plasticity, but the consequences are long-term.