Microglia play a pivotal role in neuroinflammation, which has been increasingly implicated in various neuropsychiatric disorders, including depression. Liu et al. highlight the potential of a photoresponsive CAR-M system that targets neuroinflammation to treat inflammation-related depression, emphasizing the challenge of delivering effective drugs across the blood-brain barrier (ref: Liu doi.org/10.1002/adma.202108525/). In a related study, Bennett et al. explore the interactions between microglia and their environment in human neuroimmune organoids, proposing a transcriptomic 'microglia report card' to assess microglial contributions to neurodevelopment and disease (ref: Bennett doi.org/10.1016/j.stem.2021.11.005/). Furthermore, Pluvinage et al. identify the CD22-IGF2R interaction as a therapeutic target for lysosomal dysfunction in microglia, particularly in Niemann-Pick type C disease, underscoring the vulnerability of microglia to lysosomal stress (ref: Pluvinage doi.org/10.1126/scitranslmed.abg2919/). Dodiya et al. demonstrate that gut microbiota influences amyloid beta pathology in mice through microglial modulation, suggesting a significant link between the microbiome and neuroinflammation (ref: Dodiya doi.org/10.1084/jem.20200895/). Mills et al. investigate the role of microglia in retinal vasoregulation, revealing alterations in microglial function during early diabetic retinopathy (ref: Mills doi.org/10.1073/pnas.2112561118/). Smajić et al. utilize single-cell sequencing to uncover glial activation patterns in Parkinson's disease, highlighting increased microglial presence and stress responses (ref: Smajić doi.org/10.1093/brain/). Velayudhan et al. provide a systematic review of microglial activation patterns following mild traumatic brain injury, emphasizing the need for further research to understand these dynamics (ref: Velayudhan doi.org/10.1186/s40478-021-01297-1/). Lastly, Zhang et al. reveal that an HDAC6 inhibitor can reverse chemotherapy-induced mechanical hypersensitivity via an IL-10 dependent pathway, linking microglial activity to pain modulation (ref: Zhang doi.org/10.1016/j.bbi.2021.12.005/).

Microglial involvement in neurodegenerative diseases is a burgeoning area of research, with studies highlighting their dual role in both neuroprotection and neurodegeneration. Huuskonen et al. investigate the protective effects of 3K3A-activated protein C in ischemic white matter, emphasizing the need for effective treatments for ischemic stroke, which is a significant contributor to dementia (ref: Huuskonen doi.org/10.1084/jem.20211372/). Lee et al. utilize single-cell RNA sequencing to analyze non-neuronal responses in Alzheimer’s disease models, revealing distinct microglial, oligodendrocyte, and astrocyte responses to tau and amyloid pathology, which may inform therapeutic strategies (ref: Lee doi.org/10.1016/j.celrep.2021.110158/). Santos et al. review the regulatory role of microglia in myelination, suggesting that microglial interactions with myelin are crucial for maintaining neural health throughout life (ref: Santos doi.org/10.1126/sciadv.abk1131/). Shen et al. present a novel hydrogel that releases IL-10 to promote neural regeneration post-spinal cord injury, highlighting the therapeutic potential of modulating microglial activity in injury recovery (ref: Shen doi.org/10.1016/j.biomaterials.2021.121279/). Mamais et al. explore the impact of LRRK2 mutations on microglial function in Parkinson's disease, revealing how these mutations affect iron uptake and lysosomal function (ref: Mamais doi.org/10.1371/journal.pbio.3001480/). Smit et al. discuss the dysregulation of microglial function in Alzheimer's disease, identifying specific genetic risk factors and expression profiles associated with disease progression (ref: Smit doi.org/10.1016/j.bbi.2021.12.001/). Heles et al. examine the role of chemokine CCL2 in modulating nociceptive synaptic transmission, linking microglial activity to pain management in neurodegenerative contexts (ref: Heles doi.org/10.1186/s12974-021-02335-4/). Tastan et al. investigate the effects of dimethyl fumarate on NLRP3 inflammasome activation in microglia, suggesting its potential as a treatment for inflammation-related behaviors (ref: Tastan doi.org/10.3389/fimmu.2021.737065/).

The interactions between microglia and other cell types are critical for understanding their roles in health and disease. Jackson et al. investigate the effects of different ApoE alleles on blood-brain barrier integrity, revealing that ApoE4 derived from astrocytes contributes to barrier impairment, which may have implications for neurodegenerative diseases (ref: Jackson doi.org/10.1093/brain/). Ranawat et al. explore the mechanisms of microglial colonization in the developing neural retina of zebrafish, providing insights into the developmental origins and migration pathways of microglia (ref: Ranawat doi.org/10.7554/eLife.70550/). You et al. present a new method for obtaining adult-like microglia from mice, which could enhance the study of microglial functions and their interactions with other cell types in vitro (ref: You doi.org/10.1186/s12974-021-02351-4/). Velayudhan et al. summarize the temporal patterns of microglial activation following mild traumatic brain injury, highlighting the interactions between microglia and other glial cells in response to injury (ref: Velayudhan doi.org/10.1186/s40478-021-01297-1/). Tang et al. investigate the role of the C3/C3aR pathway in microglia-astrocyte interactions during posthemorrhagic hydrocephalus, suggesting that targeting this pathway may alleviate hydrocephalus in neonatal rats (ref: Tang doi.org/10.1016/j.neuropharm.2021.108927/). Nuñez et al. demonstrate how microglial cytokines can induce invasiveness and proliferation in glioblastoma cells, indicating a complex interplay between tumor cells and the immune environment (ref: Nuñez doi.org/10.3390/cancers13246160/). Ravula et al. assess the neurobehavioral and neuropathological changes following blast-induced neurotrauma, emphasizing the role of microglia in the response to such injuries (ref: Ravula doi.org/10.1016/j.expneurol.2021.113938/).

Microglial activation is a key feature in various disease models, providing insights into their roles in neuroinflammation and neurodegeneration. Chen et al. investigate the p38-TFEB pathways in microglial activation in Parkinson's disease models, revealing that these pathways inhibit CMA-mediated NLRP3 degradation, thus promoting inflammation (ref: Chen doi.org/10.1186/s12974-021-02349-y/). Minaya et al. develop a 3D-printed cecal fistula implant for long-term access to the gut microbiome, finding no significant impact on microglial activation, which suggests that the gut-brain axis may not directly influence microglial behavior in this model (ref: Minaya doi.org/10.3390/nu13124515/). Hamner et al. demonstrate that microglial depletion abolishes ischemic preconditioning in white matter, highlighting the importance of microglial activity in neuroprotection during ischemic events (ref: Hamner doi.org/10.1002/glia.24132/). Timmerman et al. conduct transcriptome analysis to reveal the contributions of oligodendrocyte and radial glia-derived cues in maintaining microglial identity, which is crucial for understanding microglial function in health and disease (ref: Timmerman doi.org/10.1002/glia.24136/).

Therapeutic strategies targeting microglia are gaining attention as potential interventions for neurodegenerative diseases. Ravichandran et al. discuss the role of inflammasome activation in neurodegenerative diseases, emphasizing the need for early intervention strategies to mitigate neuroinflammation (ref: Ravichandran doi.org/10.1042/EBC20210021/). Frank et al. explore the neuroinflammatory responses induced by the SARS-CoV-2 spike S1 subunit, proposing that it may act as a PAMP to activate microglia and induce sickness behavior (ref: Frank doi.org/10.1016/j.bbi.2021.12.007/). Liu et al. investigate the TNF signaling pathway's role in microglial activation during acute sleep deprivation, linking microglial activity to anxiety-like behaviors (ref: Liu doi.org/10.1016/j.bbi.2021.12.006/). Saadi et al. examine the protective role of CD40L against neuroinflammatory demyelination in a mouse model of multiple sclerosis, suggesting that targeting this pathway may offer therapeutic benefits (ref: Saadi doi.org/10.1371/journal.ppat.1010059/). Minaya et al. also contribute to the understanding of gut microbiome access and its implications for microglial activation, reinforcing the need for innovative therapeutic approaches (ref: Minaya doi.org/10.3390/nu13124515/).

Microglia are essential for brain development, influencing neurogenesis and the maturation of neural circuits. Bennett et al. highlight the role of microglia in human neuroimmune organoids, proposing a 'microglia report card' to assess their contributions to neurodevelopment and disease pathogenesis (ref: Bennett doi.org/10.1016/j.stem.2021.11.005/). Huuskonen et al. discuss the neuroprotective effects of 3K3A-activated protein C in ischemic white matter, emphasizing the importance of understanding microglial roles in neuroprotection during development (ref: Huuskonen doi.org/10.1084/jem.20211372/). Shen et al. develop an IL-10-releasing hydrogel to promote neural regeneration after spinal cord injury, illustrating how microglial modulation can enhance recovery (ref: Shen doi.org/10.1016/j.biomaterials.2021.121279/). Pluvinage et al. identify the CD22-IGF2R interaction as a therapeutic target for microglial lysosome dysfunction, which is crucial for maintaining microglial health during development (ref: Pluvinage doi.org/10.1126/scitranslmed.abg2919/). Ranawat et al. explore the mechanisms of microglial colonization in the developing zebrafish retina, providing insights into their developmental origins and functions (ref: Ranawat doi.org/10.7554/eLife.70550/).

Microglia are integral to the immune response in the central nervous system, with their activation influencing various pathological conditions. Göttert et al. investigate how lithium inhibits tryptophan catabolism via the kynurenine pathway in human microglia, suggesting a potential mechanism for its mood-stabilizing effects (ref: Göttert doi.org/10.1002/glia.24123/). Huuskonen et al. examine the impact of air pollution on cerebrovascular pathology, linking particulate matter exposure to microglial activation and vascular dysfunction (ref: Huuskonen doi.org/10.3389/fimmu.2021.785519/). Wang et al. identify serum galectin-3 as a potential biomarker for post-stroke cognitive impairment, highlighting the role of microglial-derived inflammatory mediators in neurological outcomes (ref: Wang doi.org/10.1155/2021/). Minaya et al. also contribute to understanding the gut microbiome's impact on microglial activation, reinforcing the connection between peripheral immune responses and central nervous system health (ref: Minaya doi.org/10.3390/nu13124515/).

Microglial dysfunction is increasingly recognized as a contributing factor in psychiatric disorders, with studies linking inflammation to altered neurogenesis and behavior. North et al. identify a subgroup of schizophrenia patients with elevated inflammation, demonstrating reduced microglial presence and altered neurogenesis marker expression in the subependymal zone (ref: North doi.org/10.1038/s41398-021-01742-8/). Beamer et al. explore the role of the ATP-gated P2X7 receptor in microglial activation during status epilepticus, revealing how its overexpression can lead to reduced responsiveness to anticonvulsants (ref: Beamer doi.org/10.1111/bph.15785/). Nolle et al. describe a method for isolating glial cells from human post-mortem tissue, enabling the study of microglial profiles in psychiatric conditions (ref: Nolle doi.org/10.3389/fncel.2021.772011/). Defaye et al. investigate the role of gut-innervating TRPV1+ neurons in driving chronic visceral pain via microglial activation, linking peripheral and central mechanisms in inflammatory bowel diseases (ref: Defaye doi.org/10.1016/j.jcmgh.2021.12.012/). Xia et al. highlight the role of SIRT1 in promoting M2 microglia polarization, suggesting a potential therapeutic target for subarachnoid hemorrhage injury (ref: Xia doi.org/10.3389/fimmu.2021.770744/).