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Wallace, W.

Publications and source records attributed to Wallace, W..

2 recordsLinked to original sources

Placental prostaglandin signaling disrupts barrier integrity and relays an acute inflammatory signal to the fetus.

Maternal inflammation during pregnancy is a major risk factor for adverse neurodevelopmental outcomes, yet the mechanisms linking maternal immune activation (MIA) to placenta-fetal brain axis dysfunction remain unclear. Using a poly-(I:C) mouse model, we show that MIA rapidly disrupts placental-blood barrier (PBB) integrity by disrupting pericyte-endothelium coupling within 48 hours, leading to increased placental permeability detected by in vivo MRI. We identify a prostaglandin E2 (PGE2)-dependent pathway involving cyclooxygenase-2 (COX2) and prostaglandin E-synthase (mPGES1) as a key mediator of this effect. Pharmacological inhibition of COX2 prevented MIA-induced structural and functional changes. In vitro explant studies confirmed that PGE2 acts via the EP3 receptor to disrupt pericyte-endothelium interactions, while ex vivo perfusion demonstrated that in addition to its local effects on PBB structure, placenta-derived PGE2 enters the fetal circulation. Finally, similar vascular alterations were observed in human placentas from pregnancies with severe maternal inflammation. These findings reveal a conserved inflammatory mechanism that compromises PBB integrity and may relay signals to the fetal brain, highlighting potential therapeutic targets for neuroprotection during prenatal inflammation. One Sentence SummaryMaternal immune activation during pregnancy disrupts placental vascular integrity through a COX2-dependent prostaglandin E2 pathway, which compromises the placenta-blood barrier and relays inflammatory signals to the fetus, identifying potential therapeutic targets for neuroprotection.

developmental biology↗

Short Neurorobotics Workshop for High School Students Promotes Competence and Confidence in Computational Neuroscience

Understanding the brain is a fascinating challenge, captivating the scientific community and the public alike. The lack of effective treatment for most brain disorders makes the training of the next generation of neuroscientists, engineers and physicians a key concern. Over the past decade there has been a growing effort to introduce neuroscience in primary and secondary schools, however hands-on laboratories have been limited to anatomical or electrophysiological activities. Modern neuroscience research labs are increasingly using computational tools to model circuits of the brain to understand information processing. Here we introduce the use of neurorobots - robots controlled by computer models of biological brains - as an introduction to computational neuroscience in the K-12 classroom. Neurorobotics has enormous potential as an education technology because it combines multiple activities with clear educational benefits including neuroscience, active learning, and robotics. We describe an introductory neurorobot workshop that teaches high school students how to use neurorobots to investigate key concepts in neuroscience, including spiking neural networks, synaptic plasticity, and adaptive action selection. Our do-it-yourself (DIY) neurorobot uses wheels, a camera, a speaker, and a distance sensor to interact with its environment, and can be built from generic parts costing about $150 in under 4 hrs. Our Neurorobot App visualizes the neurorobot's visual input and brain activity in real-time, and enables students to design new brains and deliver dopamine-like reward signals to reinforce chosen behaviors. We have tested the Neurorobot Workshop with high school students (n = 3 workshops, 9 students total) and have found that students were able to complete all exercises in under 3 hrs. In a post-workshop survey, students reported having gained the ability to develop neural networks that perform specific functions, including goal-directed behavior and memory. Here we provide DIY hardware assembly instructions, discuss our open-source Neurorobot App and demonstrate how to teach the Neurorobot Workshop. By doing this we hope to accelerate research in educational neurorobotics and promote the use of neurorobots to teach computational neuroscience in high school.

scientific communication and education↗