TY - JOUR
T1 - Microglia at the scene of the crime
T2 - what their transcriptomics reveal about brain health
AU - Arutyunov, Artem
AU - Klein, Robyn S.
N1 - Funding Information:
This work is supported by the following grants to RSK: R01NS116788, R35NS122310, R01 AI160188 and R01AI175524-01.
Publisher Copyright:
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Purpose of review: Microglia, which arise from primitive myeloid precursors that enter the central nervous system (CNS) during early development, are the first responders to any perturbance of homeostasis. Although their activation has become synonymous with neurologic disease, it remains unclear whether microglial responses are the cause of or response to neuropathology. Here, we review new insights in the roles of microglia during CNS health and disease, including preclinical studies that transcriptionally profile microglia to define their functional states. Recent findings: Converging evidence suggests that innate immune activation of microglia is associated with overlapping alterations in their gene expression profiles regardless of the trigger. Thus, recent studies examining neuroprotective microglial responses during infections and aging mirror those observed during chronic neurologic diseases, including neurodegeneration and stroke. Many of these insights derive from studies of microglial transcriptomes and function in preclinical models, some of which have been validated in human samples. During immune activation, microglia dismantle their homeostatic functions and transition into subsets capable of antigen presentation, phagocytosis of debris, and management of lipid homeostasis. These subsets can be identified during both normal and aberrant microglial responses, the latter of which may persist long-term. The loss of neuroprotective microglia, which maintain a variety of essential CNS functions, may therefore, in part, underlie the development of neurodegenerative diseases. Summary: Microglia exhibit a high level of plasticity, transforming into numerous subsets as they respond to innate immune triggers. Chronic loss of microglial homeostatic functions may underlie the development of diseases with pathological forgetting.
AB - Purpose of review: Microglia, which arise from primitive myeloid precursors that enter the central nervous system (CNS) during early development, are the first responders to any perturbance of homeostasis. Although their activation has become synonymous with neurologic disease, it remains unclear whether microglial responses are the cause of or response to neuropathology. Here, we review new insights in the roles of microglia during CNS health and disease, including preclinical studies that transcriptionally profile microglia to define their functional states. Recent findings: Converging evidence suggests that innate immune activation of microglia is associated with overlapping alterations in their gene expression profiles regardless of the trigger. Thus, recent studies examining neuroprotective microglial responses during infections and aging mirror those observed during chronic neurologic diseases, including neurodegeneration and stroke. Many of these insights derive from studies of microglial transcriptomes and function in preclinical models, some of which have been validated in human samples. During immune activation, microglia dismantle their homeostatic functions and transition into subsets capable of antigen presentation, phagocytosis of debris, and management of lipid homeostasis. These subsets can be identified during both normal and aberrant microglial responses, the latter of which may persist long-term. The loss of neuroprotective microglia, which maintain a variety of essential CNS functions, may therefore, in part, underlie the development of neurodegenerative diseases. Summary: Microglia exhibit a high level of plasticity, transforming into numerous subsets as they respond to innate immune triggers. Chronic loss of microglial homeostatic functions may underlie the development of diseases with pathological forgetting.
KW - aging
KW - microglia
KW - neurodegeneration
KW - neuroinfectious disease
KW - transcriptome
KW - viral encephalitis
UR - http://www.scopus.com/inward/record.url?scp=85158904724&partnerID=8YFLogxK
U2 - 10.1097/WCO.0000000000001151
DO - 10.1097/WCO.0000000000001151
M3 - Article
C2 - 37078646
AN - SCOPUS:85158904724
SN - 1350-7540
VL - 36
SP - 207
EP - 213
JO - Current opinion in neurology
JF - Current opinion in neurology
IS - 3
ER -