In this review we present a concept that, despite mounting evidence , received little attention so far: susceptibility to adult neurodegenerative diseases may be programmed in utero and early postnatal preventive measures may reduce the risk. We delineate the key mechanisms and players mediating this phenomenon laying a foundation for preventive strategies. First, we discuss what is likely the most common insult taking place during fetal development and imprinting upon fetal brain: chronic pregnancy stress. We propose that such imprinting is mediated via the microglial (and perhaps astrocytic) memory and that such memory may increase susceptibility to neurodegenerative diseases in adult life. We discuss microglial plasticity and mechanisms by which in utero insults influence the dynamic process of microglial-neuronal interactions in the developing brain. Microglial role in adult neurodegenerative disorders is reviewed and this concept is brought back to the perinatal origins of adult susceptibility to neurodegeneration. We review epigenetic mechanisms which may yield early biomarkers . Can we devise novel early life modifying interventions to steer developmental trajectories to their optimum?
We review evidence supporting the role of early life programming in the susceptibility for adult neurodegenerative diseases while highlighting questions and proposing avenues for future research to advance our understanding of this fundamental process. The key elements of this phenomenon are chronic stress, neuroinflammation triggering microglial polarization, microglial memory and their connection to neurodegeneration. We review the mediating mechanisms which may function as early biomarkers of increased susceptibility for neurodegeneration . Can we devise novel early life-modifying interventions to steer developmental trajectories to their optimum?
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In this review we present a concept that, despite mounting evidence , received little attention so far: susceptibility to
We review evidence supporting the role of early life programming in the susceptibility for
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may be programmed in utero and early postnatal preventive measures may reduce the risk. We delineate the key mechanisms and players mediating this phenomenon laying a foundation for preventive strategies. First, we discuss what is likely the most common insult taking place during fetal development and imprinting upon fetal brain: chronic pregnancy stress. We propose that such imprinting is mediated via the microglial (and perhaps astrocytic) memory and that such memory may increase susceptibility to neurodegenerative diseases in adult life. We discuss microglial plasticity and mechanisms by which in utero insults influence the dynamic process of microglial-neuronal interactions in the developing brain. Microglial role in adult neurodegenerative disorders is reviewed and this concept is brought back to the perinatal origins of adult susceptibility to
while highlighting questions and proposing avenues for future research to advance our understanding of this fundamental process. The key elements of this phenomenon are chronic stress, neuroinflammation triggering microglial polarization, microglial memory and their connection to
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epigenetic
the mediating
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yield early biomarkers
function as early biomarkers of increased susceptibility for neurodegeneration
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life modifying
life-modifying