Maternal Gastrointestinal Nematode Infection Up-regulates Expression of Genes Associated with Long-Term Potentiation in Perinatal Brains of Uninfected Developing Pups

Manjurul Haque,Marilyn E Scott,Kristine G Koski

doi:10.1038/s41598-019-40729-w

Manjurul Haque, Marilyn E Scott + Show 1 more

Open Access

https://doi.org/10.1038/s41598-019-40729-w

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Journal: Scientific Reports	Publication Date: Mar 12, 2019
Citations: 8	License type: open-access

Affiliation: McGill University

Abstract

Establishment of neural networks critical for memory and cognition begins during the perinatal period but studies on the impact of maternal infection are limited. Using a nematode parasite that remains in the maternal intestine, we tested our hypothesis that maternal infection during pregnancy and early lactation would alter perinatal brain gene expression, and that the anti-inflammatory nature of this parasite would promote synaptic plasticity and long-term potentiation. Brain gene expression was largely unaffected two days after birth, but in seven-day old pups, long-term potentiation and four related pathways essential for the development of synaptic plasticity, cognition and memory were up-regulated in pups of infected dams. Interestingly, our data suggest that a lowering of Th1 inflammatory processes may underscore the apparent beneficial impact of maternal intestinal infection on long-term potentiation.

Highlights

Long-term potentiation and impaired responses to motor and cognitive tests[13]
Time series analysis provided a heatmap of the full developmental profile of brain gene expression from embryonic day 18 (E18) to postnatal day 2 (P2) to P7 in control and infected groups (Supplementary Fig. 1)
This study extends evidence of maternal effects on early brain development by revealing changes at P7 but not P2 in pup brain gene expression in response to infection with a nematode parasite that is restricted to the maternal small intestine

Summary

Introduction

Long-term potentiation and impaired responses to motor and cognitive tests[13]. In contrast, we recently explored the impact of low dose infection of pregnant mice with a nematode that is restricted to the maternal intestine and that induces anti-inflammatory Th2 responses[14]. The strong anti-inflammatory nature of this parasite is evident in Th2 responses both in the local tissue and in circulation of infected mice[17], and in the enhancement of the Th2 response over that normally observed in pregnancy[18] This infection reduces symptoms of auto-immune diseases that induce a strong inflammatory response[16]. This model is suitable for testing the intriguing possibility that an infection that remains restricted to the maternal intestine and that is known to induce a Th2 response may have a positive impact on pathways associated with long-term potentiation (Fig. 1) in the uninfected pups. We used pathway analysis and interrogated the gene expression database to determine if maternal infection altered neuro-inflammation or the cytokine environment in the pup brain on P7

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