Impact of Early Life Immune Challenges on Brain Wiring

Key Words: Neurodevelopmental and psychiatric disorders, Brain wiring, Brain development, Neuroimmune interactions, Parvalbumin inhibitory neurons, transcriptomics

Understanding what impacts the development of a child’s brain is critical for the health of children because the brain controls all aspects of their physical, cognitive, and emotional growth. The brain is not mature at birth, its development continues throughout childhood and adolescence. Therefore, negative experiences during childhood (such as exposure to toxins, stress, etc.) can have adverse effects on brain development. This can lead to a range of physical, emotional, and cognitive problems and ultimately affect a child’s long-term health and well-being. Among these negative experiences, there is the response of our immune system to infections in other parts of the body. Research has shown that the immune and nervous systems talk to each other at all ages both in health and disease. However, this communication is potentially very impactful in children because their brain is still developing and is therefore both adaptable and vulnerable.

In the project, we will test the possibility that early-life peripheral immune challenges impact child health in two ways. First, they may train parts of the brain to better respond to those challenges in the future. In children, brain cells are constantly forming new connections and strengthening existing ones to make brain circuits more efficient. For example, exposure to language and sounds during childhood refines and improves our ability to process auditory information. Similarly, we will use mice to understand if early-life immune experiences help refine neurons or circuits responsible for processing immune information. We will also study what are the cells involved, how do they communicate and what happens inside those cells. The second way in which early-life peripheral immune challenges can impact child’s health is by abnormally altering brain development. We will test if that happens when those challenges are more severe or prolonged and believe they may ultimately lead to impaired learning, poor mental health, and chronic disease in children.

Studying the impact of early life immune challenges on brain wiring is crucial for promoting healthy child development and preventing long-term negative outcomes, and can help inform policies, programs, and interventions aimed at improving the health and well-being of children.