bims-microg 2025-07-13 papers

bims-microg

Biomed News

on Microglia in health and disease

Issue of 2025–07–13
29 papers selected by
Marcus Karlstetter, Universität zu Köln

Replacing microglia to treat a brain disease.
Microglia replacement halts the progression of microgliopathy in mice and humans.
Gut microbiota-derived TMAVA is a modulator of acute CNS-GVHD.
The Alzheimer's disease-associated complement receptor 1 variant confers risk by impacting glial phagocytosis.
Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways.
Synthetic efferocytic receptor microglia enhances anti-inflammatory clearance of amyloid-β for AD treatment in mice.
Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes.
Liver-specific expression of ANGPTL8 promotes Alzheimer's disease progression through activating microglial pyroptosis.
Gut microbiota-derived indoleacetic acid attenuates neuroinflammation and neurodegeneration in glaucoma through ahr/rage pathway.
Pharmacological inhibition of the cGAS-STING pathway suppresses microglia pyroptosis in sepsis-associated encephalopathy.
Triglyceride metabolism controls inflammation and microglial phenotypes associated with APOE4.
Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1.
Alzheimer model chip with microglia BV2 cells.
Therapeutic potential of atorvastatin in ischemic stroke: an investigation into its anti-inflammatory effect by targeting the gut-brain axis.
Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.
Rethinking microglia from a circadian perspective in neuroimmunology: New insights.
Delayed microglial depletion protects against white matter injury following neonatal cerebral hemorrhage in mice.
Link between blood-brain barrier disruption and microglial activation.
Decoding microglial aging through multi-model approaches.
The niacin receptor HCAR2 prevents sleep deprivation-induced cognitive impairment by inhibiting microglia-mediated neuroinflammation in mice.
Microglia interact with dendritic spines and regulate spine numbers after brain injury following resuscitation from a cardiac arrest.
Microglial Bmal1 Contributes to Diurnal Physiology and Retinal Homeostasis.
Local microglial activation induced and labeled in the retina in a novel subretinal hemorrhage mouse model.
MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis.
Human induced pluripotent stem cell-derived microglia with a CX3CR1-V249I genetic variant exhibit dysfunctional phenotypes and modulate neuronal growth and function.
A human pluripotent stem cell tri-culture platform to elucidate microglial regulation of retinal ganglion cells in neuroinflammation.
Stimulation of α7 Nicotinic Acetylcholine Receptors by PNU282987 Demonstrates Efferocytosis-Like Activation and Neuroprotection in Human Models of Microglia and Cholinergic Neurons under the Pathophysiological Conditions of Alzheimer's Disease.
Cryptococcus neoformans and Microglia In Vitro Interaction as a Tool to Study Central Nervous System Infection.
Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation.

Science. 2025 Jul 10. 389(6756): 129-130

Replacing microglia to treat a brain disease.

Siling Du, Jonathan Kipnis.

Swapping out the brain's immune cells can slow progression of a devastating neurological disease.

DOI: https://doi.org/10.1126/science.adz0113
Science. 2025 Jul 10. 389(6756): eadr1015

Microglia replacement halts the progression of microgliopathy in mice and humans.

Jingying Wu, Yafei Wang, Xiaoyu Li, Pei Ouyang, Yuanyuan Cai, Yang He, Mengyuan Zhang, Xinghua Luan, Yuxiao Jin, Jie Wang, Yujie Xiao, Yuqing Liang, Fang Xie, Yousheng Shu, Jiong Hu, Chunkang Chang, Jieling Jiang, Dong Wu, Youshan Zhao, Taohui Liu, Yuxin Li, Xiaojun Huang, Yao Li, Junfang Zhang, Yuwen Cao, Xin Cheng, Ying Mao, Yanxia Rao, Li Cao, Bo Peng.

Colony-stimulating factor 1 receptor (CSF1R) is primarily expressed in microglia. Its monoallelic mutation causes CSF1R-associated microgliopathy (CAMP), a major form of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and a fatal neurological disease without clinical cure. We developed mouse models harboring human hotspot mutations of CAMP and replaced CSF1R-deficient microglia with CSF1R-normal cells through microglia replacement by bone marrow transplantation (Mr BMT), which attenuated pathology in mice. We further demonstrated that, in the context of CSF1R deficiency, traditional bone marrow transplantation (tBMT) in ALSP functions similarly to Mr BMT, efficiently replacing microglia and reducing disease progression. We then replaced CSF1R-deficient microglia in eight patients by tBMT. The disease progression was halted during the 24-month follow-up. Together, microglia replacement corrects pathogenic mutations and halts disease progression in mice and humans.

DOI: https://doi.org/10.1126/science.adr1015
J Exp Med. 2025 Sep 01. pii: e20242180. [Epub ahead of print]222(9):

Gut microbiota-derived TMAVA is a modulator of acute CNS-GVHD.

Sangya Chatterjee, Tamina Rückert, Ina Martin, Elisa Michaeli, Joerg Buescher, Petya Apostolova, Daniel Erny, Maria-Eleni Lalioti, Francesca Biavasco, Alina Hartmann, Solveig Runge, Lukas M Braun, Nana Talvard-Balland, Rachael C Adams, Annette Schmitt-Graeff, James Cook, Valentin Wenger, Dimitrios Athanassopoulos, Dilara Hasavci, Alexander Paolo Vallejo-Janeta, Thomas Blank, Philipp Schaible, Janaki Manoja Vinnakota, Alexander Zähringer, Stephanie C Ganal-Vonarburg, Wolfgang Melchinger, Dietmar Pfeifer, Natalie Köhler, Stephan P Rosshart, David Michonneau, Gérard Socié, Geoffroy Andrieux, Nina Cabezas-Wallscheid, Melanie Boerries, Marco Prinz, Robert Zeiser.

Acute graft-versus-host disease (aGVHD) can affect the central nervous system (CNS) through microglial activation and T cell infiltration, but the role of gut microbiota in CNS-aGVHD remains unclear. Here, we investigated the role of microbiota in microglial activation during aGVHD using antibiotic-treated specific pathogen-free (SPF), germ-free (GF), and wildling mice. Antibiotic-mediated microbiota depletion led to infiltration of IFN-γ-producing T cells in the brain, activation of microglia via the TLR4/p38 MAPK pathway, and neurocognitive deficits in SPF aGVHD mice. Microglial depletion reversed the neurocognitive deficits. GF and wildling mice treated with antibiotics exhibited similar microglial activation after allogeneic hematopoietic cell transplantation (allo-HCT). Mechanistically, the bacteria-derived metabolite N,N,N-trimethyl-5-aminovaleric acid (TMAVA) was decreased in microglia following antibiotic treatment. TMAVA administration suppressed TLR4/p38 MAPK pathway activity in microglia and alleviated gut microbiota depletion-mediated neurocognitive deficits. Additionally, TMAVA abundance decreased in patient blood after allo-HCT and after GVHD onset. In summary, we identify TMAVA loss as a central causative factor for CNS-aGVHD, opening new perspectives for a metabolite-based therapy.

DOI: https://doi.org/10.1084/jem.20242180
Alzheimers Dement. 2025 Jul;21(7): e70458

The Alzheimer's disease-associated complement receptor 1 variant confers risk by impacting glial phagocytosis.

Nikoleta Daskoulidou, Bethany Shaw, Wioleta Milena Zelek, Bryan Paul Morgan.

   INTRODUCTION: Genome-wide association studies have implicated complement in Alzheimer's disease (AD). The CR1*2 variant of complement receptor 1 (CR1; CD35), confers increased AD risk. We confirmed CR1 expression on glial cells; however, how CR1 variants influence AD risk remains unclear.
METHODS: Induced pluripotent stem cell-derived microglia and astrocytes were generated from donors homozygous for the common CR1 variants (CR1*1/CR1*1;CR1*2/CR1*2). CR1 expression was quantified and phagocytic activity assessed using diverse targets (Escherichia coli bioparticles, amyloid β aggregates, and synaptoneurosomes), with or without serum opsonization.
RESULTS: Expression of CR1*1 was significantly higher than CR1*2 on glial lines. Phagocytosis for all targets was markedly enhanced following serum opsonization, attenuated by Factor I-depletion, demonstrating CR1 requirement for C3b processing. CR1*2-expressing glia showed significantly enhanced phagocytosis of all opsonized targets compared to CR1*1-expressing cells.
DISCUSSION: CR1 is critical for glial phagocytosis of opsonized targets. CR1*2, despite lower expression, enhances glial phagocytosis, providing mechanistic explanation of increased AD risk.
HIGHLIGHTS: Induced pluripotent stem cell (iPSC)-derived glia from individuals expressing the Alzheimer's disease (AD) risk variant complement receptor (CR) 1*2 exhibit lower CR1 expression compared to those from donors expressing the non-risk form CR1*1. The iPSC-derived glia from individuals expressing the AD risk variant CR1*2 exhibit enhanced phagocytic activity for opsonized bacterial particles, amyloid-β aggregates and human synaptoneurosomes compared to those from donors expressing the non-risk form CR1*1. We suggest that expression of the CR1*2 variant confers risk of AD by enhancing the phagocytic capacity of glia for opsonized targets.

Keywords:  Alzheimer's; CR1; astrocytes; complement; microglia; opsonization; phagocytosis

DOI:  https://doi.org/10.1002/alz.70458
Sci Adv. 2025 Jul 11. 11(28): eadv5986

Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways.

Lujuan He, Xuenan Wang, Shilin Luo, Nan Jiang, Yu Yan, Min Xie, Yueyue Chen, Chun Yang, Wei Yao, Kenji Hashimoto, Ji-Chun Zhang.

Arketamine, the (R)-enantiomer of (R,S)-ketamine, shows even greater rapid and sustained antidepressant-like effects in rodent models compared to esketamine, yet the underlying mechanisms remain unclear. In this study, we used the chronic social defeat stress (CSDS) model to investigate how arketamine exerts its antidepressant-like effects. We found that activating cAMP response element-binding protein (CREB) at S133 and methyl-CpG-binding protein 2 (MeCP2) at S421 drives the transcription of brain-derived neurotrophic factor (BDNF), contributing to arketamine's antidepressant-like effects. Furthermore, microglia-derived BDNF enhances excitatory synaptic transmission in the infralimbic (IL) region of the medial prefrontal cortex (mPFC), mediating the antidepressant-like effects of arketamine in CSDS-susceptible mice. Last, microglia-derived BDNF can activate mPFC (IL) neurons projecting to the nucleus accumbens (NAc) shell, contributing to arketamine's antidepressant-like effects. These findings highlight the essential role of microglial BDNF in modulating NAc-projecting mPFC neurons, which contribute to the antidepressant-like effects of arketamine.

DOI: https://doi.org/10.1126/sciadv.adv5986
Sci Adv. 2025 Jul 11. 11(28): eads6613

Synthetic efferocytic receptor microglia enhances anti-inflammatory clearance of amyloid-β for AD treatment in mice.

Lijuan Shao, Yi Zhang, Zhenmei Yang, Chongdeng Shi, Xiao Yue, Caiping Li, Ying Liu, Zhipeng Fu, Chunwei Tang, Xiaotian Zhao, Maosen Han, Jing Zhang, Weiyi Sun, Zichao Yao, Kaiyan Xi, Zezheng Fang, Zixu Wang, Fan Feng, Chunhong Ma, Kun Zhao, Yulin Zhang, Shilei Ni, Xinyi Jiang, Chen Chen.

Monoclonal antibody immunotherapy targeting the clearance of amyloid-β (Aβ) has shown promise in Alzheimer's disease (AD). However, current antibody treatments trigger Fc receptors and induce proinflammatory responses, in turn exacerbating neuronal damage. Here, we report a synthetic efferocytic receptor (SER) integrating Aβ-targeting scFv, efferocytosis receptor backbone based on TIM4 and downstream signal for microglia (MG) reprogramming, which enabled selective elimination of Aβ without inducing an inflammatory response. Specifically, our in-house-customized MG-editing mRNA lipid nanoparticles (MERLINs) efficiently introduced SER mRNA into MG to generate Aβ-specific SER-MG in situ. SER-MG exhibited robust Aβ-specific phagocytosis and stimulated anti-inflammatory efferocytosis typical signaling in vitro. In a mouse model of AD, SER expression in the MG markedly increased the clearance of Aβ and dampened inflammation, resulting in improved behavioral outcomes along with substantially reduced synapse elimination. Our findings establish that AD-associated aberrant MG can be in situ reprogrammed with SER for Aβ clearance in an anti-inflammatory manner, with broad application in other inflammation-related diseases.

DOI: https://doi.org/10.1126/sciadv.ads6613
Mol Psychiatry. 2025 Jul 10.

Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes.

Ashutosh Tripathi, Alona Bartosh, Dania Jose, Jocelyn Mata, Usama Hussein, Fernanda Laezza, Zhongming Zhao, Anilkumar Pillai.

The social deficits following chronic stress conditions are linked to synaptic dysfunction in the brain. Complement system plays a critical role in synapse regulation. Although complement has been implicated in chronic stress-induced behavior deficits the cellular substrates and mechanisms underlying complement-mediated behavior changes under chronic stress conditions are not known. In the present study, we investigated the role of complement component 3a receptor (C3ar1) in microglia and monocytes/macrophages (Mo/MΦ) in chronic unpredictable stress (CUS)-induced synapse loss and behavior deficits in mice. We found that deletion of microglial C3ar1 attenuated stress-induced social behavior deficits and changes in neuroinflammatory as well as synaptic markers in the prefrontal cortex (PFC). RNA sequencing data revealed that microglial C3ar1 deletion attenuates CUS-mediated changes in the expression of immediate-early genes such as Fos and Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) in the PFC. In contrast, lack of C3ar1 in Mo/MΦ induced social behavior deficits. Together, these findings indicate opposite functions of C3ar1 signaling in microglia and Mo/MΦ under chronic stress conditions.

DOI: https://doi.org/10.1038/s41380-025-03097-8
J Neuroinflammation. 2025 Jul 09. 22(1): 177

Liver-specific expression of ANGPTL8 promotes Alzheimer's disease progression through activating microglial pyroptosis.

Jiarui Wei, Lin Hu, Shufan Xu, Fan Yang, Fusheng Liao, Ying Tang, Xin Shen, Xiaoqiao Zhang, Xinggang Fang, Yifan Li, Li Ding, Zhuo Chen, Shanchun Su, Junhua Cheng, Yong Huang, Qian Chen, Daqing Ma, Qiufang Zhang, Xingrong Guo.

   INTRODUCTION: Liver dysfunction contributes to Alzheimer's disease (AD) pathogenesis, and evidence suggests that the liver is involved in amyloid β (Aβ) clearance, and regulates Aβ deposition in the brain. However, the specific regulatory mechanism remains elusive.
OBJECTIVES: Angiopoietin-like protein 8 (ANGPTL8), a high expression of liver-specific secreted proinflammatory factor, crosses the blood‒brain barrier from the bloodstream to abnormally activate microglia and promote AD progression.
METHODS: The ANGPTL8-/- mice and 5 × FAD mice were crossed mutated and subjected to the Morris water maze test and novel object recognition test to assess cognitive ability in different cohorts. Thioflavin-S, NeuN, and Nissl staining were used to assess Aβ deposition and neuron loss. The number of phagocytic microglia was evaluated with Fitc latex beads. Adeno-associated virus 8 (AAV8) hydrodynamically injected restored the liver ANGPTL8 levels of ANGPTL8-/- 5 × FAD mice for further experiments. Single-cell RNA sequencing, bulk RNA sequencing and transmission electron microscopy were used to explore the role of ANGPTL8 in regulating AD progression, and drug screening was carried out to identify an effective inhibitor of ANGPTL8.
RESULTS: ANGPTL8 knockout improved cognitive function and reduced Aβ deposition by reducing microgliosis and microglial activation in 5xFAD mice. Mechanistically, ANGPTL8 crossed the blood‒brain barrier and interacted with the microglial membrane receptor PirB/LILRB2. This interaction subsequently activated the downstream NLRP3 inflammasome, leading to microglial pyroptosis and exacerbating the Aβ-induced release of inflammatory factors, thereby accelerating AD progression. Furthermore, the administration of metformin, an ANGPTL8 inhibitor, improved learning and memory deficits in 5 × FAD mice by negating microglial pyroptosis and neuroinflammation.
CONCLUSIONS: ANGPTL8 aggravates microglial pyroptosis via the PirB/NLRP3 pathway to accelerate the pathogenesis of AD. Targeting high expression of ANGPTL8 in the liver may hold potential for developing therapies for AD.

Keywords:  ANGPTL8; Alzheimer's disease; Liver‒brain axis; Microglial pyroptosis; Neuroinflammation

DOI:  https://doi.org/10.1186/s12974-025-03487-3
J Neuroinflammation. 2025 Jul 10. 22(1): 179

Gut microbiota-derived indoleacetic acid attenuates neuroinflammation and neurodegeneration in glaucoma through ahr/rage pathway.

Ning Wang, Chengyang Sun, Yijie Yang, Dandan Zhang, Lulu Huang, Chenrui Xu, Minghan Wang, Mengmeng Xu, Tongtong Yan, Yue Wu, Li Xu, Yahan Ju, Hao Sun, Wenyi Guo.

   BACKGROUND: Gut microbiota has emerged as a promising therapeutic target for neurodegenerative disorders through regulation of neuroinflammatory responses, while its role in optic nerve degeneration remains incompletely characterized. This study elucidates the neuroprotective role of gut microbiota derived tryptophan metabolites in glaucoma through gut-eye communication and inhibition of microglia-mediated neuroinflammation.
METHODS: Gut microbiota profiling (16 S rRNA sequencing) and serum indoleacetic acid (IAA) quantification were performed in glaucoma patients versus controls. Microbiota-metabolite relationships were further validated through fecal microbiota transplantation (FMT). The neuroprotective and anti-neuroinflammatory effect of Bacteroides fragilis (B. fragilis) and IAA was assessed in both microbead-induced ocular hypertension mice model and in vitro BV-2 microglial cell inflammation model via immunofluorescence, qPCR, Western blot and mice behavioral assays. To explore the underlying mechanisms, retinal transcriptomics and microglia-neuron co-cultures were also employed.
RESULT: Glaucoma patients exhibited gut dysbiosis characterized by depleted tryptophan-metabolizing bacteria (B. fragilis, Bacteroides thetaiotaomicron, Anaerostipes hadrus) and reduced serum IAA levels. Mice receiving FMT from glaucoma patients exhibited lower systemic IAA levels. In in vivo and in vitro models, B. fragilis or IAA restored AhR activation, suppressed inflammation by inhibiting microglial activation and the release of pro-inflammatory mediators throughout the retina, reduced retinal ganglion cells (RGCs) loss and preserved visual function. Mechanistically, IAA attenuated RAGE/NF-κB pathway activation via AhR-dependent signaling, conferring neuroprotection.
CONCLUSION: Our study proposes a novel AhR-mediated gut microbiota-eye axis in glaucoma pathogenesis and demonstrates that IAA serves as an effective neuroprotective strategy with clinical potential for managing RGCs neurodegeneration.

Keywords:  AhR; Glaucoma; Gut microbiota-eye axis; Microglia; Neuroinflammation; Tryptophan metabolites

DOI:  https://doi.org/10.1186/s12974-025-03505-4
J Neuroinflammation. 2025 Jul 09. 22(1): 176

Pharmacological inhibition of the cGAS-STING pathway suppresses microglia pyroptosis in sepsis-associated encephalopathy.

Qing-Quan Zeng, Yang Qi, Hui Yu, Ying Xu, Jin-Xing Chen, You-Wei Zheng, Gui-Fei Zhang, Qiao-Ling Zhang, Yan-Hua Zheng, Jing Guo, Zi-Hong Zhao, Fa-Sheng Wang, Gui-Lin Jin.



Keywords:  Microglia; Pyroptosis; STING; Sepsis; Sepsis-associated encephalopathy

DOI:  https://doi.org/10.1186/s12974-025-03507-2
Cell Rep. 2025 Jul 10. pii: S2211-1247(25)00732-6. [Epub ahead of print]44(7): 115961

Triglyceride metabolism controls inflammation and microglial phenotypes associated with APOE4.

Roxan A Stephenson, Jordy Sepulveda, Kory R Johnson, Adrian Lita, Jaanam Gopalakrishnan, Dominic J Acri, Alexandra Beilina, Linling Cheng, Linda G Yang, Jessica T Root, Michael E Ward, Christian Combs, William C Skarnes, Mark R Cookson, Han-Yu Shih, Mioara Larion, G William Rebeck, Priyanka S Narayan.

  Changes to cellular lipids accompany shifts in microglial cell state, but the functional significance of these metabolic changes remains poorly understood. In human induced pluripotent stem cell-derived microglia, we observed that both extrinsic activation (by lipopolysaccharide treatment) and intrinsic triggers (the Alzheimer's disease-associated APOE4 genotype) result in accumulation of triglyceride-rich lipid droplets. We demonstrate that lipid droplet accumulation is not simply concomitant with changes in the cell state. In fact, both triglyceride biosynthesis and catabolism are critical for the activation-induced transcription and secretion of inflammatory cytokines and chemokines, as well as changes in phagocytosis. In microglia harboring the Alzheimer's disease risk APOE4 genotype, inhibiting triglyceride biosynthesis attenuates disease-associated transcriptional states. Triglyceride biosynthesis inhibition also rescues microglial surveillance defects observed in slices from APOE4 humanized transgenic mice. Together, our findings establish that modulating triglyceride metabolism can tune microglial immune activity in response to extrinsic activation and in APOE4-associated disease.

Keywords:  APOE; Alzheimer's; CP: Neuroscience; activation; disease; iPSCs; lipid droplets; lipid metabolism; microglia; motility; neuroinflammation; triglycerides

DOI:  https://doi.org/10.1016/j.celrep.2025.115961
Aging Cell. 2025 Jul 07. e70167

Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1.

Kai Liu, Di Fan, Hai-Peng Wu, Xiao-Yi Hu, Qiu-Li He, Xin-Miao Wu, Cui-Na Shi, Jian-Jun Yang, Mu-Huo Ji.

  Microglia-mediated neuroinflammation has been shown to exert an important effect on the progression of a growing number of neurodegenerative disorders. Prolonged exposure to detrimental stimuli leads to a state of progressive activation and aging-related features in microglia (also termed as senescent microglia). However, the mechanisms by which senescent microglia contribute to neuroinflammation-induced cognitive dysfunction remain to be elucidated. Here, we developed a mouse model of neuroinflammation induced by lipopolysaccharides at 0.5 mg/kg for 7 consecutive days. To evaluate cognitive function, C57BL/6J mice were employed and subjected to a series of behavioral assessments, including the open field, Y-maze, and novel object recognition tests. Employing single-cell RNA sequencing technology, we have delved into the differential expressions of RNA within microglia. Furthermore, to investigate anatomic and physiological alterations of pyramidal neurons, we utilized Golgi staining and whole-cell patch-clamp recordings, respectively. Validation of our results in protein expression was performed using western blotting and immunofluorescence. We specifically identified senescent microglia with a high expression of p16INK4a and observed that microglia in the hippocampal CA1 region of the model exhibited signatures of elevated phagocytosis and senescence. A senolytic by ABT-737 treatment alleviated the production of senescence-associated secretory phenotypes, the accumulation of senescent microglia, and the microglial hyperphagocytosis of excitatory synapses following LPS exposures. This treatment also restored reduced excitatory synaptic transmission, impaired long-term potentiation, and cognitive function in the model. These results indicate that reducing senescent microglia may potentially serve as a therapeutic approach to prevent neuroinflammation-related cognitive dysfunction.

Keywords:  long‐term potentiation; microglia; neuroinflammation; senescence; synaptic plasticity

DOI:  https://doi.org/10.1111/acel.70167
Microsyst Nanoeng. 2025 Jul 08. 11(1): 135

Alzheimer model chip with microglia BV2 cells.

Ehsan Yazdanpanah Moghadam, Nahum Sonenberg, Muthukumaran Packirisamy.

Amyloid beta oligomers (AβO) are pivotal in Alzheimer's Disease (AD), cleared by microglia cells, as immune cells in the brain. Microglia cells exposed to AβO are involved with migration, apoptosis, phagocytosis, and activated microglial receptors through AβO, impacting cellular mechanobiological characteristics such as microglial adhesion strength to the underlying substrate. Herein, a label-free microfluidic device was used to detect advancing AD conditions with increasing AβO concentrations on microglia BV2 cells by quantitatively comparing the cell-substrate adhesion. The microfluidic device, acting as an AD model, comprises a single channel, which functions as a cell adhesion assay. To assess cell-substrate adhesion under different AβO concentrations of 1 µM, 2.5 µM, and 5 µM, the number of the cells attached to the substrate was counted by real-time microscopy when the cells were under the flow shear stress of 3 Pa and 7.5 Pa corresponding to Reynolds number (Re) of 10 and 25, respectively. The data showed that quantifying the cell-substrate adhesion using the microfluidic device could successfully identify conditions of advancing AβO concentrations. Our findings indicated that the increased incubation time with AβO caused reduced cell-substrate adhesion strength. Additionally, increased AβO concentration was another factor that weakened microglial interaction with the substrate. The quantification of cell-substrate adhesion using 3 Pa compared to 7.5 Pa clearly demonstrated advancing AβO in AD. This study using the chip provides an AD model for a deeper understanding mechanobiological behaviors of microglia exposed to AβO corresponding to diagnosed AD conditions under an in vitro microenvironment.

DOI: https://doi.org/10.1038/s41378-024-00862-7
J Transl Med. 2025 Jul 08. 23(1): 750

Therapeutic potential of atorvastatin in ischemic stroke: an investigation into its anti-inflammatory effect by targeting the gut-brain axis.

Liuzhu Chen, Linpei Zhuo, Jie Zheng, Xiaoyun Sun, Jing Sun, Jiaming Liu.

   BACKGROUND: Recent studies have highlighted the vital role of gut microbiota in the pathogenesis of Ischemic stroke (IS). However, the effects and underlying mechanisms of atorvastatin on IS via regulating gut-brain axis remain unclear. Thus, this study aimed to explore the relationship between atorvastatin, gut microbiota and IS through animal experiments, clinical trials and Mendelian randomization (MR) analysis.
METHODS: Male mice were induced with bilateral common carotid artery occlusion (BCCAO) to establish an IS animal model, and then intragastrically treated with atorvastatin. Neurological deficits, microglia activation, and the levels of NLRP3 inflammasome and NF-κB pathway-related proteins were detected. Meanwhile, gut microbiota composition and intestinal barrier integrity were evaluated. In this prospective study, we recruited IS patients undergoing atorvastatin treatment, evaluated their functional outcomes, collected fecal samples, and assessed gut microbiota functions. Moreover, the causal relationships between specific bacteria, inflammation and IS were assessed via MR analysis.
RESULTS: Our results showed that atorvastatin treatment significantly improved neurobehavioral deficits, suppressed activation of microglia, and inhibited NF-κB pathway as well as the formation of the NLRP3 inflammasome, reduced the release of inflammatory cytokines, including IL-1β and IL-18, which were reversed by antibiotics treatment. We further identified an increase in the genus Lachnospiraceae NK4A136 in atorvastatin-treated mice. Subsequent clinical experiments were conducted to explore the effects by analyzing the characteristic bacteria, such as Ruminococcus torques and Lachnospiraceae NK4A136. The higher abundances of Ruminococcus torques and Lachnospiraceae NK4A136 were associated with a good outcome in atorvastatin-treated IS patients. MR analysis further revealed that these microbes were negatively correlated with inflammatory factor levels, and showed inhibitory effects on the Akt/NF-κB/NLRP3 pathway and PLA2G7 gene expression.
CONCLUSION: These findings demonstrated the roles of atorvastatin in regulating Akt/NF-κB/NLRP3 pathway to inhibit neuroinflammation through specific bacteria, which implied a novel way for IS treatment.

Keywords:  Atorvastatin; Gut microbiota; Ischemic stroke; NF-κB pathway; NLRP3 inflammasome; Neuroinflammation

DOI:  https://doi.org/10.1186/s12967-025-06803-w
J Headache Pain. 2025 Jul 10. 26(1): 158

Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.

Yin Xu, Xinli Liu, Hui Chen, Yun Zhao, Yubai Zhao, Yu Xie, Jiahui Pang, Hui Zeng, Yanyan Zeng, Weiwei Peng, Manxu Zheng, Wen Wu.



Keywords:  Clec7a; Microglia; Neuroinflammation; Neuropathic pain; Phagocytosis; Spi1

DOI:  https://doi.org/10.1186/s10194-025-02089-x
Neural Regen Res. 2025 Jul 05.

Rethinking microglia from a circadian perspective in neuroimmunology: New insights.

Daniele Mattei.

DOI: https://doi.org/10.4103/NRR.NRR-D-25-00157
Neural Regen Res. 2025 Jul 05.

Delayed microglial depletion protects against white matter injury following neonatal cerebral hemorrhage in mice.

Xiaoxiao Jing, Xiaoli Zhang, Hongwei Li, Yu Yang, Zuhang Zhao, Yuandan Li, Jinjin Zhu, Yiran Xu, Jing Yuan, Tiantian He, Chen Zhang, Juan Song, Xin Zhao, Xiaoyang Wang, Changlian Zhu, Falin Xu.

  Germinal matrix hemorrhage in preterm neonates often leads to white matter injury, contributing to long-term neurodevelopmental impairments. As resident brain immune cells, microglia play a complex role in injury response, including inflammation and repair. Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia, their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored. Here, we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice, and intraperitoneally administered PLX5622 72 hours post- germinal matrix hemorrhage to achieve targeted, temporary microglial depletion during the peak injury response. We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation, white matter integrity, and neurobehavioral outcomes. Additionally, RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions. RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage, thus pinpointing the critical response phases for potential interventions. Delayed PLX5622 treatment effectively depleted activated microglia, protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions. Moreover, magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice. Behaviorally, PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice. These findings suggest that, when timed to avoid interference with initial oligodendrocyte lineage cell proliferation, targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage. The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.

Keywords:  PLX5622; colony-stimulating factor 1 receptor; germinal matrix hemorrhage; microglia; myelination; neonatal brain; oligodendrocyte lineage cell; white matter injury

DOI:  https://doi.org/10.4103/NRR.NRR-D-24-01400
Neural Regen Res. 2025 Jul 05.

Link between blood-brain barrier disruption and microglial activation.

Arjun Sapkota, Sebok K Halder, Richard Milner.

DOI: https://doi.org/10.4103/NRR.NRR-D-25-00103
Neural Regen Res. 2025 Jun 19.

Decoding microglial aging through multi-model approaches.

Martin Škandík, Bertrand Joseph.

DOI: https://doi.org/10.4103/NRR.NRR-D-25-00229
Int Immunopharmacol. 2025 Jul 04. pii: S1567-5769(25)01164-6. [Epub ahead of print]162 115174

The niacin receptor HCAR2 prevents sleep deprivation-induced cognitive impairment by inhibiting microglia-mediated neuroinflammation in mice.

Zhaoyan Cheng, Tengda Qian, Jiaqi Yu, Yuhui Yan, Lijia Jing, Baowei Yang, Huiling Tang, Aiwen Yan, Mengqi Liu, Yuewen Song, Jing Dai.

  Sleep loss has become a common occurrence nowadays, posing significant concerns to public health by increasing risks of various diseases. Studies have shown that sleep loss can cause neuroinflammation and cognitive decline, yet its exact mechanisms and reliable prevention strategies remain unclear. Hydroxycarboxylic acid receptor 2 (HCAR2) is a G protein-coupled receptor expressed in various immune cells, and its activation shows beneficial anti-inflammatory effects in some peripheral and central inflammatory diseases. In this study, we aimed to employ a sleep deprivation (SD) mouse model, combined with genetic and pharmacological manipulation, behavioral tests, biochemical assays and proteomics analysis, to investigate whether activation of HCAR2 could improve SD-induced neuroinflammation and cognitive impairment in mice. We observed that SD significantly disrupted HCAR2 signaling, activated NF-κB/NLRP3 signaling pathway, promoted microglial M1 polarization and ensuing neuroinflammation, impaired synaptic plasticity in the hippocampus of mice, and thereby resulted in cognitive deficits. However, activating HCAR2 with niacin effectively reversed these changes and ultimately alleviated SD-induced cognitive impairment in mice. Our findings suggest that the impaired HCAR2 signaling may be one of the pathogenesis mechanisms of SD, and HCAR2 may represent a promising therapeutic target for sleep loss-related cognitive disorders.

Keywords:  Cognitive impairment; HCAR2; Microglia; Neuroinflammation; Sleep deprivation

DOI:  https://doi.org/10.1016/j.intimp.2025.115174
Exp Neurol. 2025 Jul 05. pii: S0014-4886(25)00228-6. [Epub ahead of print]392 115364

Microglia interact with dendritic spines and regulate spine numbers after brain injury following resuscitation from a cardiac arrest.

Jacob M Basak, Macy Falk, Andra L Dingman, Annabelle Moore, Erika Tiemeier, Giulia Aimale, Nidia Quillinan.

  Cognitive dysfunction is common after global cerebral ischemic injury caused by a cardiac arrest and is likely due in part to changes in synaptic function. Increasing evidence suggests microglial cells regulate synapse architecture and activity in various pathophysiologic conditions. However, the role of microglia in mediating synaptic injury after global cerebral ischemia has not been addressed. In this study, we use a mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to evaluate changes that occur in the numbers and morphology of both dendritic spines and microglia in the hippocampus after global cerebral ischemia. We also directly evaluate the interaction between dendritic spines and microglia after CA/CPR and assess how altering microglial numbers after the injury affects spine numbers. Our findings highlight that CA/CPR results in hippocampal spine loss that occurs in parallel with an increase in microglia numbers. Morphologic analysis of microglial cells demonstrates that CA/CPR leads to acute changes in cellular structure consistent with reactivity to the ischemic injury. We also show that microglia-spine contacts increase in the period following a CA/CPR injury along with co-localization between spines and phagocytic vesicles within microglia, suggesting a potential role for microglial engulfment in mediating spine loss. Finally, we demonstrate that pharmacologic depletion of microglia with PLX5622 after CA/CPR restores spine numbers in the injured brain. Collectively, these results emphasize the important role microglia exhibit in regulating synapse numbers in the setting of a CA/CPR injury and suggest targeting microglia-synapse interactions may improve cognitive outcomes following global ischemic brain injury.

Keywords:  Cardiac arrest; Dendritic spines; Global cerebral ischemia; Microglia; PLX5622; Phagocytosis

DOI:  https://doi.org/10.1016/j.expneurol.2025.115364
Glia. 2025 Jul 11.

Microglial Bmal1 Contributes to Diurnal Physiology and Retinal Homeostasis.

Charles W Pfeifer, Andrea Santeford, Rajendra S Apte.

  Circadian rhythms govern various physiological processes, including innate and adaptive immune responses. Microglia, the sentinels of the central nervous system (CNS), mediate synaptic remodeling and local immune responses that contribute to tissue homeostasis. Recent studies have uncovered that microglial surveillance behavior and cytokine production exhibit rhythmicity. Furthermore, disruption of clock gene expression in microglia impairs phagocytic capacity, metabolism, and inflammatory responses, suggesting that their dynamic functions are regulated in part by circadian rhythms. Given the growing recognition of circadian dysregulation in disease pathophysiology, elucidating molecular mechanisms of microglial chronobiology may reveal novel therapeutic strategies to resynchronize circadian rhythms with components of the immune system. Homeostatic rhythms and the implications of their disruption have yet to be explored in microglia that reside within the neurosensory retina, a tissue in the back of the eye that initiates visual transduction and relays photic information to the brain. In this study, we demonstrate that retinal microglia express rhythms in clock gene expression, morphology, and inflammatory markers that rely on the clock gene Bmal1. We also find that loss of Bmal1 in microglia is associated with a decline in retinal health and behavioral dysfunction in the mouse. Lastly, we demonstrate that Bmal1 deficiency also induces a senescent, disease-associated phenotype in microglia and transcriptomic reprogramming in the retinal parenchyma. These findings suggest that diurnal clock rhythms regulate microglia physiology within the retinal niche and contribute to homeostatic maintenance of the local tissue environment.

Keywords:  circadian; eye; microglia; neuroimmunology; physiology; retina

DOI:  https://doi.org/10.1002/glia.70061
Sci Rep. 2025 Jul 10. 15(1): 24804

Local microglial activation induced and labeled in the retina in a novel subretinal hemorrhage mouse model.

Boglárka Balogh, Marietta Zille, Gergely Szarka, Loretta Péntek, Anett Futácsi, Béla Völgyi, Tamás Kovács-Öller.

  Subretinal hemorrhage (SRH) is caused by the accumulation of blood between the neurosensory retina and the retinal pigment epithelium or between the retinal pigment epithelium and the choroid. SRH often arises from age-related macular degeneration, traumas, and may occur spontaneously caused by other diseases like hypertension and diabetes. Here, we developed a novel technique - co-injection of blood and a dye-coupled tracer protein, Cholera toxin subunit B (CtB) - to better localize and understand the disease and how it can cause microglial activation, inflammation, and partial vision loss. Our results show that microglia are activated in the inner retinal layers in zones adjacent to blood injection. In contrast, the non-affected zone of the injected eye showed no microglial activation. For the first time, we used phosphate-buffered saline (PBS) injections as a control to assess the specific effects of injected blood. The results demonstrated that blood induced a markedly stronger activation response in the surrounding tissue, whereas PBS elicited a comparatively milder effect. PBS did cause microglial activation, but it was largely confined to the injection site and adjacent regions, and to a lesser extent than that observed with blood. We also observed microglial activation in the inner retina, along with the emergence of microglia and macrophages in the retinal pigment epithelium. Using advanced imaging techniques, we were able to better localize the affected area which comprises not only the immediate retinal area over the blood clot but the neighboring regions as well. These findings will provide the basis for novel therapeutic interventions targeting neuroinflammation in the retina after subretinal hemorrhage and other diseases affecting the eye.

Keywords:  Bleeding; Blood; Cholera toxin; Experimental ophthalmology; Eye; Inflammation; Retinal pigment epithelium

DOI:  https://doi.org/10.1038/s41598-025-09007-w
Cell Mol Neurobiol. 2025 Jul 07. 45(1): 63

MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis.

Elmira Roshani Asl, Seyedeh Elnaz Hosseini, Fatemeh Tahmasebi, Nadia Bolandi, Shirin Barati.

  Multiple sclerosis (MS) is a chronic inflammatory disease associated with demyelination and microglial activation. Significant progress has recently been made in the development of strategies to treat MS with a focus on microglial cells. In response to injury, microglia, a population of mononuclear phagocytic cells, change from quiescent to activated. M1 microglia produce pro-inflammatory cytokines that cause additional injury, thus they are considered neurotoxic microglia. M2 microglia release anti-inflammatory factors that lead to the suppression of inflammatory responses; therefore, they have a neurotrophic phenotype. The balance between M1 and M2 phenotypes is important for nerve recovery. In neurodegenerative diseases, activated microglia are excessively shifted toward M1 or neurotoxic phenotype due to microRNA (miRNA) dysregulation. The miRNA as a class of non-coding RNAs, control the neuroinflammatory process by activation of microglia. The miR-124 is partly responsible for suppressing the neuroprotective and inflammatory processes by preventing microglia activation. Meanwhile, the microRNA 155, which is induced by pro-inflammatory agents in microglia, promotes the inflammatory process. Several studies have shown that in MS pathogenesis, miR-124 as an anti-inflammatory marker is significantly downregulated, while miR-155 shows an increase. In this study, we will investigate the role of miR-124 and miR-155 in the activation and alteration of microglial phenotype. Finding the relationship between microRNAs and glial cells and inflammation in MS may be used as a therapeutic method to reduce the symptoms in MS patients.

Keywords:  MiR-124; MiR-155; Microglia; Multiple sclerosis

DOI:  https://doi.org/10.1007/s10571-025-01578-6
bioRxiv. 2025 Jul 04. pii: 2025.07.01.662163. [Epub ahead of print]

Human induced pluripotent stem cell-derived microglia with a CX3CR1-V249I genetic variant exhibit dysfunctional phenotypes and modulate neuronal growth and function.

Kaylee D Tutrow, Jade Harkin, Laurna Varghese, Melody Hernandez, Kang-Chieh Huang, Yue Fang, Parker Wilcox, Logan Bedford, Tsai-Yu Lin, Chi Zhang, Cátia Gomes, Shweta Puntambekar, Stephanie Bissel, Bruce T Lamb, Jason S Meyer.

The involvement of microglia in neurodegenerative diseases has drawn increasing attention, as many genetic risk factors are preferentially expressed in microglia. Microglial fractalkine receptor (CX3CR1) signaling regulates many key microglial functions, and the CX3CR1-V249I single nucleotide polymorphism (SNP) has been associated with increased risk for multiple neurodegenerative conditions, including Alzheimer's disease, yet its functional consequences in human microglia remain unexplored. In this study, we generated iPSC-derived human microglia-like cells (hMGLs) and found that the CX3CR1-V249I variant increased susceptibility to starvation-induced cell death, reduced amyloid-beta uptake, altered microglial morphology, and impaired migration, with more pronounced effects in homozygous cells. Co-culture with neurons demonstrated that hMGLs with the CX3CR1-V249I variant misregulated neuronal properties, including abnormal neuronal growth as well as an induction of neuronal hyperexcitability. These findings highlight the critical role of CX3CR1 in regulating microglial function and implicate the V249I variant in driving pathogenic microglial states relevant to neurodegeneration.

DOI: https://doi.org/10.1101/2025.07.01.662163
bioRxiv. 2025 Jul 04. pii: 2025.07.01.662573. [Epub ahead of print]

A human pluripotent stem cell tri-culture platform to elucidate microglial regulation of retinal ganglion cells in neuroinflammation.

Jade Harkin, Cátia Gomes, Kaylee D Tutrow, Reham Afify, Shruti V Patil, Kiersten H Peña, Aaron Baker, Sailee S Lavekar, Kang-Chieh Huang, Jason S Meyer.

Optic neuropathies, including glaucoma, are characterized by the progressive degeneration of retinal ganglion cells (RGCs), ultimately leading to irreversible vision loss. Increasing evidence implicates microglia, the resident immune cells of the central nervous system, as key modulators of RGC health and disease progression. However, the precise mechanisms by which microglia influence RGCs remain poorly understood, particularly in the human context. In this study, we established human pluripotent stem cell (hPSC)-derived co-culture systems incorporating microglia, astrocytes, and RGCs to explore how microglia shape RGC growth and maturation under physiological conditions. We first examined the impact of homeostatic microglia on RGCs in both co-culture and tri-culture systems, revealing distinct influences of cell types in co-culture compared to when they were grown individually. We then modeled inflammatory states by activating microglia with lipopolysaccharide (LPS) and evaluated their effects on RGCs both directly and in the context of astrocyte co-culture. This stepwise, reductionist approach enabled us to dissect the cellular interactions driving RGC vulnerability in inflammatory conditions relevant to optic neuropathies. Our findings provide new insight into the complex neuroimmune landscape that underlies RGC degeneration and identify key pathways that may serve as therapeutic targets across a range of optic nerve diseases.

DOI: https://doi.org/10.1101/2025.07.01.662573
Biol Pharm Bull. 2025 ;48(7): 972-985

Stimulation of α7 Nicotinic Acetylcholine Receptors by PNU282987 Demonstrates Efferocytosis-Like Activation and Neuroprotection in Human Models of Microglia and Cholinergic Neurons under the Pathophysiological Conditions of Alzheimer's Disease.

Mari Sueyoshi, Koki Harada, Masaki Okawa, Teruki Matsuhara, Momona Ando, Riona Araki, Yuka Minote, Keiichi Ishihara, Shun Shimohama, Kazuyuki Takata.

  Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) peptide accumulation, leading to neuroinflammation and neurodegeneration. In early AD stages, neurodegeneration of basal forebrain cholinergic neurons occurs. Microglia, which are brain immune cells, contribute to Aβ clearance and neuroinflammation. This study investigated the therapeutic effects of PNU282987, a selective full agonist of α7 nicotinic acetylcholine receptor (nAChR), using human models of microglia (hiMacs) and basal forebrain cholinergic neurons (hiBFChNs), both differentiated from human induced pluripotent stem cells (hiPSCs). Our findings indicated that PNU282987 markedly enhanced Aβ phagocytosis by microglia and extracellular Aβ clearance. Furthermore, PNU282987 injection reduced Aβ accumulation in the brain of a mouse model. Treatment of hiMacs with PNU282987 upregulated the expressions of efferocytosis-related genes, such as ASAP2, OSM, and THBD. Efferocytosis-like activation by PNU282987 in hiMacs was further suggested by an increased release of the anti-inflammatory cytokine interleukin-10 (IL-10), along with suppression of the pro-inflammatory cytokine IL-1β produced from microglia with Aβ treatment. This indicates a transformation from Aβ-induced inflammatory phagocytosis to an efferocytosis-like anti-inflammatory phagocytosis. PNU282987 also exerted direct neuroprotective effects on hiBFChNs against Aβ and tumor necrosis factor-α. Furthermore, PNU282987 changed the extracellular contents released from Aβ-treated hiMacs and attenuated the neurotoxicity. These results suggest that α7 nAChR stimulation by PNU282987 enhances the therapeutic effects against AD by promoting Aβ clearance with anti-neuroinflammatory regulation in the microglia and providing direct protection to neurons, thereby addressing the inflammatory and neurodegenerative aspects of AD.

Keywords:  basal forebrain; full agonist; human induced pluripotent stem cell; neuroinflammation; primitive macrophage

DOI:  https://doi.org/10.1248/bpb.b25-00308
Methods Mol Biol. 2025 ;2950 167-178

Cryptococcus neoformans and Microglia In Vitro Interaction as a Tool to Study Central Nervous System Infection.

Patrícia Albuquerque, André Moraes Nicola, Hugo Costa Paes.

  This chapter presents in vitro protocols for studying interactions between Cryptococcus neoformans and microglial cells. These phagocytes are a critical component of the central nervous system's immune response to C. neoformans, the most common fungal agent of meningoencephalitis worldwide. Given its severity and high incidence in immunocompromised patients, understanding the interaction of C. neoformans with central nervous system (CNS) cells could help advance treatment strategies. These protocols leverage microscopy and molecular biology techniques to elucidate the mechanisms of C. neoformans invasion and persistence within the CNS, offering a methodological framework for fungal neuropathogenesis research.

Keywords:  Central nervous system; Cryptococcus neoformans; Host-pathogen interaction; Microglia; Phagocytosis

DOI:  https://doi.org/10.1007/978-1-0716-4674-8_11
J Vis Exp. 2025 Jun 17.

Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation.

Chenyuan Zhai, Jili Cai, Mei Du, Yuchen Fei, Qi Wu.

Microglia, the resident phagocytes of the central nervous system (CNS), play a pivotal role in maintaining CNS integrity and homeostasis by removing damaged cells, cellular debris, and myelin remnants. The accumulation of myelin debris is implicated in a range of CNS disorders, including multiple sclerosis, Alzheimer's disease, traumatic brain injury, and spinal cord injury. The presence of myelin debris not only exacerbates neuroinflammation but also hampers the regenerative potential of myelin. Therefore, enhancing the ability of microglia to clear myelin debris through phagocytosis represents a promising therapeutic strategy. Magnetic stimulation has emerged as an innovative treatment modality for CNS diseases, with growing evidence suggesting its potential to promote microglial phagocytosis and support CNS recovery. To further elucidate the effects of magnetic stimulation on microglial clearance of myelin debris, we designed an in vitro experiment involving the co-culture of microglia and myelin debris. The co-culture was subjected to repetitive magnetic stimulation to assess its impact on microglial phagocytic activity in the context of CNS pathology.

DOI: https://doi.org/10.3791/67642