Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Humann, Jessica; Mann, Beth; Gao, Geli; Moresco, Philip; Ramahi, Joseph S.; Loh, Lip Nam; Farr, A.; Hu, Yunming; Durick-Eder, Kelly; Fillon, Sophie; Smeyne, Richard J.; Tuomanen, Elaine

doi:10.1016/j.chom.2016.02.009

Cited by 83 publications

(79 citation statements)

References 53 publications

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“…Bacterial cell wall components can also affect offspring: PG can cross the placenta and reach the fetal brain, where it induces proliferation of neurons in the frontal cortex, via increased expression of FOXG1 , a critical regulator of forebrain development and neurogenesis. Offspring exposed to PG prenatally exhibit decreased cognitive function (Humann et al, 2016). Exposure to other microbial products prenatally and neonatally has impacts on offspring behavior.…”

Section: Major Processes In Neurodevelopment Coincide With Changes Inmentioning

confidence: 99%

The Central Nervous System and the Gut Microbiome

Sharon

Sampson

Geschwind

et al. 2016

Cell

1,144

797

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Summary Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggests communication between the gut and the brain in anxiety, depression, cognition and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain-barrier, myelination, neurogenesis, and microglia maturation, and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome, and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system, and the balance between mental health and disease.

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Section: Major Processes In Neurodevelopment Coincide With Changes Inmentioning

confidence: 99%

The Central Nervous System and the Gut Microbiome

Sharon

Sampson

Geschwind

et al. 2016

Cell

1,144

797

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“…CW crossed the placenta without significant inflammation, cell death or placental dysfunction [11] . Within 24 hours, CW accumulated in the fetal brain.…”

Section: Cw Silently Crosses the Placenta And Fetal Blood Brain Barriermentioning

confidence: 99%

“…heterodimer TLR2/6 or TLR1/2 [11] . Synthetic agonists of TLR2/6 but not TLR2/1 caused neuroproliferation suggesting that CW induced signaling may be restricted to a specific arm of the classical innate immune response pathway.…”

Section: The Mechanism Of Cw Induced Neuroproliferationmentioning

confidence: 99%

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Blood borne: Bacterial components in mother’s blood influence fetal development

Loughran

Tuomanen

2016

Inflamm Cell Signal

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Bacterial or viral infection of the mother during the course of pregnancy can cross the placenta and actively infect the fetus. However, especially for bacteria, it is more common for mothers to experience an infection that can be treated without overt fetal infection. In this setting, it is less well understood what the risk to fetal development is, particularly in terms of neurological development. This research highlight reviews recent findings indicating that bacterial components generated during infection of the mother can cross the placenta and activate the fetal innate immune system resulting in changes in the course of brain development and subsequent progression to postnatal cognitive disorders. Bacterial cell wall is a ubiquitous bacterial PAMP (pathogen-associated molecular pattern) known to activate inflammation through the stimulation of TLR2. Cell wall is released from bacteria during antibiotic treatment and new work shows that embryos exposed to cell wall from the mother demonstrate anomalous proliferation of neuronal precursor cells in a TLR2 dependent manner. Such proliferation increases the neuronal density of the cortical plate and alters brain architecture. Although there is no fetal death, subsequent cognitive development is significantly impaired. This model system suggests that bacterial infection of the mother and its treatment can impact fetal brain development and requires greater understanding to potentially eliminate a risk factor for cognitive disorders such as autism.

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“…The vast amount of CW pieces released during infection greatly stimulates the host inflammatory response by activating the innate immune receptor, Toll like receptor 2 (TLR2) (Yoshimura et al , 1999). Responses differ depending on the organ infected: the postnatal brain undergoes apoptosis, scarring predominates in heart, and the fetal brain escapes damage, showing striking neuroproliferation (Orihuela et al , 2006; Braun et al , 1999; Fillon et al , 2006; Humann et al , 2016). …”

Section: Introductionmentioning

confidence: 99%

Preparation of Purified Gram-positive Bacterial Cell Wall and Detection in Placenta and Fetal Tissues

et al. 2016

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Cell wall is a complex biopolymer on the surface of all Gram-positive bacteria. During infection, cell wall is recognized by the innate immune receptor Toll-like receptor 2 causing intense inflammation and tissue damage. In animal models, cell wall traffics from the blood stream to many organs in the body, including brain, heart, placenta and fetus. This protocol describes how to prepare purified cell wall from Streptococcus pneumoniae, detect its distribution in animal tissues, and study the tissue response using the placenta and fetal brain as examples.

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Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Cited by 83 publications

References 53 publications

The Central Nervous System and the Gut Microbiome

The Central Nervous System and the Gut Microbiome

Blood borne: Bacterial components in mother’s blood influence fetal development

Preparation of Purified Gram-positive Bacterial Cell Wall and Detection in Placenta and Fetal Tissues

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