Maternal Infection Induces Neuronal Structure and Behavioural Alterations in Experimental Meningitis Rat Model.

Abstract

Introduction: Maternal infection (MI) can result in significant neurodevelopmental abnormalities and long-term neurological sequelae in offspring. This study was designed to investigate MI-induced alterations in synaptic protein expression, axonal morphology, dendritic, and spine morphology, and behaviour in a neonatal rat model of bacterial meningitis.

Methods: On gestational day 10, pregnant rats were randomly assigned to the following groups: (1) control (Ctrl), (2) MI (pregnant rats were infected with Cronobacter sakazakii by rectovaginal colonization), (3) MI +matrix metalloproteinase inhibitor (MI+MMPI) (C. sakazakii infected pregnant rats received a MMP-9 inhibitor). Male offspring from experimental groups were examined in the novel odor recognition (NOR) test on postnatal day (PND) 15 and the tail suspension test (TST) on PND-60.

Results: Offspring from the MI group were impaired in NOR and exhibited depressive behaviour during TST, whereas MI+MMPI group responses were comparable to the Ctrl group. In addition, MI upregulated the expression of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), MMP-9, and nuclear factor erythroid 2-related factor 2 (Nrf2) in their offspring. In turn, MI downregulating Na+/K+-ATPase activity, postsynaptic density protein (PSD)-95, and multiple ankyrin repeat domain protein (SHANK3) altered the conversion of mature brain-derived neurotrophic factor precursor to mature (mBDNF). Further, MI induced bending and shortening of pyramidal neuronal axon length, reduced dendritic branching complexity, and alerted dendritic and spine morphology. Treatment with MMPI minimized these MI-induced effects.

Conclusion: MI can cause microstructural rearrangements in the developing brain and behavioural deficits. Our experimental model mimics the neurological sequelae of neonatal meningitis and could be useful for developing therapeutic strategies.