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Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits
Rosa C Paolicelli1,2, Maria T Ferretti1,2
1IREM, Institute for Regenerative Medicine, University of ZurichZürich, Switzerland.
Abstract:
Many diverse factors, ranging from stress to infections, can perturb brain homeostasis and alter the physiological activity of microglia, the immune cells of the central nervous system. Microglia play critical roles in the process of synaptic maturation and brain wiring during development. Any perturbation affecting microglial physiological function during critical developmental periods could result in defective maturation of synaptic circuits. In this review, we critically appraise the recent literature on the alterations of microglial activity induced by environmental and genetic factors occurring at pre- and early post-natal stages. Furthermore, we discuss the long-lasting consequences of early-life microglial perturbation on synaptic function and on vulnerability to neurodevelopmental and psychiatric disorders.
Insights
Early-life stress and infections disrupt microglia, the brain's immune cells, impacting synaptic development. This can lead to long-term neurodevelopmental and psychiatric disorders.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia, the central nervous system's immune cells, are crucial for synaptic maturation.
- Environmental and genetic factors can disrupt microglial function during critical developmental windows.
- Perturbations in early life can lead to long-lasting consequences for brain health.
Purpose of the Study:
- To review recent literature on microglial activity alterations in early life.
- To examine the impact of environmental and genetic factors on microglia.
- To discuss the long-term effects of early microglial dysfunction on synaptic function and disorder vulnerability.
Main Methods:
- Critical appraisal of existing scientific literature.
- Synthesis of findings on environmental and genetic influences on microglia.
- Analysis of consequences for neurodevelopmental and psychiatric disorders.
Main Results:
- Diverse factors (stress, infections) perturb microglial homeostasis.
- Early-life microglial alterations can impair synaptic circuit maturation.
- These early disruptions are linked to increased vulnerability to disorders.
Conclusions:
- Early-life microglial perturbations have significant, lasting impacts on brain function.
- Understanding these early events is key to addressing neurodevelopmental and psychiatric disorders.
- Targeting early microglial responses may offer therapeutic potential.
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