The Impact of Juvenile Microglia Transcriptomics on the Adult Brain Regeneration after Cerebral Ischemia.

Abstract

Microglial cells play a pivotal role in the brain's health and operation through all stages of life and in the face of illness. The contributions of microglia during the developmental phase of the brain markedly contrast with their contributions in the brain of adults after injury. Enhancing our understanding of the pathological mechanisms that involve microglial activity in brains as they age and in cerebrovascular conditions is crucial for informing the creation of novel therapeutic approaches. In this work we provide results on microglia transcriptomics in the juvenile vs injured adult brain and its impact on adult brain regeneration after cerebral ischemia. During fetal brain development, microglia cells are involved in gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis, neurogenesis and synaptic reorganization by engulfing neuronal extensions. Within the mature, intact brain, microglial cells exhibit reduced movement of their processes in response to minimal neuronal activity, while they continuously monitor their surroundings and clear away cellular debris. Following a stroke in the adult brain, inflammation, neurodegeneration, or disruptions in neural equilibrium trigger alterations in both the genetic blueprint and the structure and roles of microglia, a state often described as "activated" microglia. Such genetic shifts include a notable increase in the pathways related to phagosomes, lysosomes, and the presentation of antigens, coupled with a rise in the expression of genes linked to cell surface receptors. We conclude that a comparison of microglia transcriptomic activity during brain development and post-stroke adult brain might provide us with new clues about how neurodegeneration occurs in the adult brain. This information could very useful to develop drugs to slow down or limit the post-stroke pathology and improve clinical outcome.