Explore the vast range of titles available.

Microglia dynamically survey the brain parenchyma. Microglial processes interact with neuronal elements; however, what role neuronal network activity plays in regulating microglial dynamics is not entirely clear. Most studies of microglial dynamics use either slice preparations or in vivo imaging in anesthetized mice. Here we demonstrate that microglia in awake mice have a relatively reduced process area and surveillance territory and that reduced neuronal activity under general anesthesia increases microglial process velocity, extension and territory surveillance. Similarly, reductions in local neuronal activity through sensory deprivation or optogenetic inhibition increase microglial process surveillance. Using pharmacological and chemogenetic approaches, we demonstrate that reduced norepinephrine signaling is necessary for these increases in microglial process surveillance. These findings indicate that under basal physiological conditions, noradrenergic tone in awake mice suppresses microglial process surveillance. Our results emphasize the importance of awake imaging for studying microglia–neuron interactions and demonstrate how neuronal activity influences microglial process dynamics.

Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention.

Microglia are resident immune cells of the central nervous system and play key roles in brain homeostasis. During anesthesia, microglia increase their dynamic process surveillance and interact more closely with neurons. However, the functional significance of microglial process dynamics and neuronal interaction under anesthesia is largely unknown. Using in vivo two-photon imaging in mice, we show that microglia enhance neuronal activity after the cessation of isoflurane anesthesia. Hyperactive neuron somata are contacted directly by microglial processes, which specifically colocalize with GABAergic boutons. Electron-microscopy-based synaptic reconstruction after two-photon imaging reveals that, during anesthesia, microglial processes enter into the synaptic cleft to shield GABAergic inputs. Microglial ablation or loss of microglial β2-adrenergic receptors prevents post-anesthesia neuronal hyperactivity. Our study demonstrates a previously unappreciated function of microglial process dynamics, which enable microglia to transiently boost post-anesthesia neuronal activity by physically shielding inhibitory inputs. Using in vivo two-photon imaging and electron microscopy, Haruwaka, Ying et al. show that microglia transiently boost post-anesthesia neuronal activity in somatosensory cortex by physically shielding inhibitory inputs during emergence from anesthesia.

Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in pain. However, there has not been direct evidence showing that selective microglial activation in vivo is sufficient to induce chronic pain. Here, we used optogenetic approaches in microglia to address this question employing CX3CR1 creER/+ : R26 LSL-ReaChR/+ transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia. We found that activation of ReaChR by red light in spinal microglia evoked reliable inward currents and membrane depolarization. In vivo optogenetic activation of microglial ReaChR in the spinal cord triggered chronic pain hypersensitivity in both male and female mice. In addition, activation of microglial ReaChR up-regulated neuronal c-Fos expression and enhanced C-fiber responses. Mechanistically, ReaChR activation led to a reactive microglial phenotype with increased interleukin (IL)-1β production, which is likely mediated by inflammasome activation and calcium elevation. IL-1 receptor antagonist ( IL-1ra ) was able to reverse the pain hypersensitivity and neuronal hyperactivity induced by microglial ReaChR activation. Therefore, our work demonstrates that optogenetic activation of spinal microglia is sufficient to trigger chronic pain phenotypes by increasing neuronal activity via IL-1 signaling.

Neuromyelitis optica (NMO) is an autoantibody-triggered neuro-inflammatory disease which preferentially attacks the spinal cord and optic nerve. Its defining autoantibody is specific for the water channel protein, aquaporin‐4 (AQP4), which primarily is localized at the end-feet of astrocytes. Histopathology studies of early NMO lesions demonstrated prominent activation of microglia, the resident immune sentinels of the central nervous system (CNS). Significant microglial reactivity is also observed in NMO animal models induced by introducing AQP4-IgG into the CNS. Here we review the potential roles for microglial activation in human NMO patients as well as different animal models of NMO. We will focus primarily on the molecular mechanisms underlying microglial function and microglia-astrocyte interaction in NMO pathogenesis. Understanding the role of microglia in NMO pathology may yield novel therapeutic approaches for this disease.

Background Neuromyelitis Optica (NMO) is a neuroimmune disorder primarily driven by autoantibodies against aquaporin 4 (AQP4), known as NMO-IgG. Although the mechanisms underlying NMO-IgG-induced retinopathy are not fully understood, the high expression of AQP4 in retinal Müller cells suggests a direct interaction that may trigger inflammatory processes in the retina. Previous studies indicate that microglia play a critical role in mediating immune responses, leading to neuronal dysfunction. Methods NMO-IgG obtained from clinical patients was administered via intravitreal injection to female C57BL/6 mice. Techniques such as optical coherence tomography (OCT), Flash Visual Evoked Potential (f-VEP), electroretinography (ERG), real-time fluorescence quantitative PCR (RT-qPCR), and immunofluorescence analyses were used to assess retinal changes. The potential for reversing retinopathy was explored by depleting microglial cells using the CSF1 receptor inhibitor PLX3397. Additionally, a Transwell co-culture system of MIO-M1 (Müller cells) and BV2 (microglia) cells was established to study their interactions. Results Intravitreal injection of purified NMO-IgG in mouse models led to its deposition in the retina and downregulation of AQP4 in provided. Vascular leakage was observed, alongside retinal dysfunction characterized by thinning of the retinal nerve fiber layer (RNFL) and loss of retinal ganglion cells (RGCs). On day 7, C3 expression was upregulated in Müller cells, followed by microglial activation. Significant morphological changes in microglia were noted, with increased expression of iNOS and C1q, indicating substantial activation. Ablating microglia significantly mitigated NMO-IgG-induced injury to RGCs. In vitro, NMO-IgG-treated MIO-M1 cells secreted higher levels of C3, enhancing the activation and migration of BV2 cells compared to controls. Conclusions The retinal dysfunction observed in NMO may primarily be linked to the activation of Müller cells by NMO-IgG, leading to increased C3 secretion, which in turn activates microglia. Therapeutic strategies targeting Müller cell–microglia interactions in NMO-IgG-induced retinopathy could be promising in addressing the underlying retinal pathology in this condition.

Sleep disturbances, including insomnia and abnormal sleep duration, are increasingly recognized for their role in various inflammatory processes, yet their causal impact on inflammatory skin diseases remains unclear. This study aims to systematically explore the causal relationships between specific 8 sleep traits and 4 inflammatory skin diseases, including psoriasis, acne, atopic dermatitis, and urticaria. We conducted a two-sample Mendelian randomization (MR) analysis using genetic data from the UK Biobank and FinnGen. Genetic variants associated with the sleep traits, such as insomnia, sleep duration, daytime sleepiness, daytime napping, snoring, and chronotype, were selected as instrumental variables. We employed methods including inverse variance weighting, weighted median estimation, and MR Egger regression to ensure robust causal inference. Sensitivity analyses were conducted to assess heterogeneity and pleiotropy. Notably, frequent insomnia was causally linked to an increased risk of psoriasis and atopic dermatitis, while longer sleep duration showed protective effects against acne and urticaria. Additionally, there was no strong evidence connecting other sleep traits like daytime sleepiness, napping, snoring, and chronotype to these skin conditions. Sensitivity analyses also confirmed the robustness and consistency of these findings across different methods. This study provides evidence that specific sleep traits, especially insomnia and sleep duration, have a causal impact on inflammatory skin diseases. Addressing sleep disturbances in dermatological care could be crucial for reducing disease severity and enhancing patient outcomes.

Antimicrobial resistance has evolved into one of the most serious threats to global public health, yet generalizable routes for refining random peptide mixtures (RPMs) into defined, stimuli‐responsive, and low‐cost antimicrobial formulations remain limited. Here, a refinement framework is presented. It centers on machine learning and co‐assembly that converts broad‐spectrum RPMs into interpretable antimicrobial peptide cocktails without exhaustive screening. Specifically, starting from a 10‐mer Arg/Leu RPM (RL0.5), its antimicrobial activity and self‐assembly are quantified, and machine learning is used to prioritize key functional peptides. Leveraging synergistic and co‐assembly behaviors, an optimal combination (AEP) is selected. The resulting defined formulation, RL10, achieves a fourfold increase in in vitro activity against Escherichia coli and exhibits a reduced critical aggregation concentration relative to the starting RPM. Overall, this study presents a practical path from complex, low‐cost precursors to efficient, co‐assembling antimicrobial cocktails, and summarizes explainable design rules that support engineering and industrialization. Machine learning refines random peptide mixtures into responsive antimicrobial cocktails, yielding enhanced antibacterial efficacy and improved in vivo therapeutic effects.

Lucilia shenyangensis Fan, 1965 (Diptera: Calliphoridae) is of potential importance in epidemiology, veterinary medicine, and forensic entomology due to their necrophilous habit and behaviors associated with mammals. In this study, we report the complete mitochondrial genome (mitogenome) of L. shenyangensis. The mitogenome is 14,989 bp in length, comprising 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and a non-coding control region. The arrangement of genes is identical to that of the ancestral metazoan. Nucleotide composition revealed a high A/T bias, accounting for 76.50% total mitogenome nucleotides (A 39.2%, G 9.6%, C 14.0%, T 37.3%). Phylogenetic analysis indicated that L. shenyangensis was clear separated from other blow flies and emerged as the sister lineage to the rest species from genus Lucilia (L. illustris, L. sericata, L. coeruleiviridis, and L. porphyrina). The mitogenome data of L. shenyangensis could facilitate further evolutionary genetic researches on blow flies.

The kuruma shrimp Marsupenaeus japonicus is one of the most commercially important shrimp species in the world. Low salinity would affect the penetration and immunity, and even led to its death of the shrimp. However, little is known about the molecular mechanism of the effect. Therefore, hepatopancreas of M. japonicus reared under low-salinity stress for 6, 12, 24, 48, and 96 h was analyzed and the results were compared with that of the control group using transcriptomics. After removing reads containing adapters, 88 890 960–1 051 300 444 clean reads were generated from 10 libraries in the control group and experimental group. Compared with the control group, 811, 589, 1 095, 745, and 875 differentially expressed genes were obtained in the five treatment groups. The N50 and N90 lengths of the transcripts were 1 746 bp and 436 bp, respectively. The top 20 gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways associated with the differentially expressed genes were related mainly to osmotic regulation (ion exchange, lipid metabolism and carbohydrate metabolism), immune regulation (cellular and humoral immunity), chitin metabolism, and related functions. The differential expression patterns of nine randomly selected genes were confirmed by quantitative real-time PCR. This is the first report of osmotic regulation-related genes that are differentially expressed under low-salinity stress in the hepatopancreas of M. japonicus . Furthermore, we found that M. japonicus initiated its own immune regulation under low-salinity stress. These results will help elucidating the mechanism of osmotic regulation and immune responses in this shrimp species.