Established and emerging techniques for the study of microglia: visualization, depletion, and fate mapping.

The central nervous system (CNS) is an essential hub for neuronal communication. As a major component of the CNS, glial cells are vital in the maintenance and regulation of neuronal network dynamics. Research on microglia, the resident innate immune cells of the CNS, has advanced considerably in recent years, and our understanding of their diverse functions continues to grow. Microglia play critical roles in the formation and regulation of neuronal synapses, myelination, responses to injury, neurogenesis, inflammation, and many other physiological processes. In parallel with advances in microglial biology, cutting-edge techniques for the characterization of microglial properties have emerged with increasing depth and precision. Labeling tools and reporter models are important for the study of microglial morphology, ultrastructure, and dynamics, but also for microglial isolation, which is required to glean key phenotypic information through single-cell transcriptomics and other emerging approaches. Strategies for selective microglial depletion and modulation can provide novel insights into microglia-targeted treatment strategies in models of neuropsychiatric and neurodegenerative conditions, cancer, and autoimmunity. Finally, fate mapping has emerged as an important tool to answer fundamental questions about microglial biology, including their origin, migration, and proliferation throughout the lifetime of an organism. This review aims to provide a comprehensive discussion of these established and emerging techniques, with applications to the study of microglia in development, homeostasis, and CNS pathologies.

Sex differences of microglia in the healthy brain from embryonic development to adulthood and across lifestyle influences.

Microglia, the central nervous system innate immune cells, play a critical role in maintaining a homeostatic environment in the brain throughout life. These cells exhibit an impressive range of functions and characteristics that help to ensure proper functioning of the brain. Notably, microglia can present differences in their genetic and physical traits, which can be influenced by a range of factors, including age, environmental exposures, disease, and sex. Remarkably, microglia have been found to express receptors for sex hormones, suggesting that these hormones may play a role in modulating microglial behavior and potentially contribute to sex differences. Additionally, sex-chromosomal factors were shown to impact microglial genetics and functioning. In this review, we will examine how microglial responses in homeostasis are impacted by their interaction with sex hormones and sex chromosomes. Specifically, our investigation will focus on examining this interaction from embryonic development to adulthood, and the influence of lifestyle elements on various microglial features, including density and distribution, morphology, transcriptome, and proteome.

The implication of a diversity of non-neuronal cells in disorders affecting brain networks.

In the central nervous system (CNS) neurons are classically considered the functional unit of the brain. Analysis of the physical connections and co-activation of neurons, referred to as structural and functional connectivity, respectively, is a metric used to understand their interplay at a higher level. A myriad of glial cell types throughout the brain composed of microglia, astrocytes and oligodendrocytes are key players in the maintenance and regulation of neuronal network dynamics. Microglia are the central immune cells of the CNS, able to affect neuronal populations in number and connectivity, allowing for maturation and plasticity of the CNS. Microglia and astrocytes are part of the neurovascular unit, and together they are essential to protect and supply nutrients to the CNS. Oligodendrocytes are known for their canonical role in axonal myelination, but also contribute, with microglia and astrocytes, to CNS energy metabolism. Glial cells can achieve this variety of roles because of their heterogeneous populations comprised of different states. The neuroglial relationship can be compromised in various manners in case of pathologies affecting development and plasticity of the CNS, but also consciousness and mood. This review covers structural and functional connectivity alterations in schizophrenia, major depressive disorder, and disorder of consciousness, as well as their correlation with vascular connectivity. These networks are further explored at the cellular scale by integrating the role of glial cell diversity across the CNS to explain how these networks are affected in pathology.