Bilbo, Staci, 2014, Early Life Immune Challenge, Primed Microglia and Neurodevelopmental Disorders.
Presentation to Autism Society, Canada.
Presentation to Autism Society, Canada.
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Staci Bilbo summarizes her Harvard University (formerly Duke University) lab's work since 2005 on the impact of early life (perinatal) immune challenge on microglia form and function both in the immediate perinatal context and also over the life of the animal
An ill-timed perinatal immune challenge which occurs at a time early in life when microglia have yet to adopt the mature form and function will leave microglia in a permanently juvenile state. Unlike normal adult microglia with small cell bodies, and long, thin, motile arm-like processes, these stunted microglia retain throughout life an amoeboid, macrophage-like form and transcriptional profile -- such that they are "primed" for life to over-react to a subsequent (second hit) immune challenge -- an overreaction leading to poor behavioral outcomes including cognitive/memory impairment, social deficits, perseverative behaviors impacting new learning ability, indicators of anxiety and depression, all of which are associated with neuro-developmental and neural network disorders such as autism and schizophrenia. Further, her work shows that pharmacological modulation of microglia during initial perinatal immune challenge fully protects the animal from microglia priming, preventing vulnerability to consequences of a second hit, and negative neurodevelopmental consequences. She also shows that prophylactic pharmacological modulation of microglia at time of second hit is also protective, even if microglia were primed perinatally. |