The Latest Articles on Microglia and Neurodegenerative Diseases
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Microglia and Neurodegenerative Diseases.
Title: Molecular and metabolic heterogeneity of astrocytes and microglia
Authors: Philip Hasel, William H. Aisenberg, F. Chris Bennett, Shane A. Liddelow
Type: Review
Abstract:
Astrocytes and microglia are central players in a myriad of processes in the healthy and diseased brain, ranging from metabolism to immunity. The crosstalk between these two cell types contributes to pathology in many if not all neuroinflammatory and neurodegenerative diseases. Recent advancements in integrative multimodal sequencing techniques have begun to highlight how heterogeneous both cell types are and the importance of metabolism to their regulation. We discuss here the transcriptomic, metabolic, and functional heterogeneity of astrocytes and microglia and highlight their interaction in health and disease.
Access this article: https://doi.org/10.1016/j.cmet.2023.03.006
Title: An active fraction from Spatholobus suberectus dunn inhibits the inflammatory response by regulating microglia activation, switching microglia polarization from M1 to M2 and suppressing the TLR4/MyD88/NF-κB pathway in LPS-stimulated BV2 cells
Authors: Molu Ban, Hua Su, Xianbiao Zeng, Chunxia Chen, Shuguang Zhou, Xiaoyu Chen, Xiaoyu Chen
Type: Research Article
Abstract:
Neurodegenerative disorders are known to be associated with neuroinflammation caused by microglia. Therefore, regulation of microglia activation and polarization to inhibit neuroinflammatory reactions seems to hold promise as a therapeutic approach in neurodegenerative disorders. Spatholobus suberectus Dunn (SSD) has been utilized as a traditional Chinese medicine remedy for brain diseases for thousands of years. SSD possesses various pharmacological activities, such as circulation invigoration, neuroprotection, and anti-inflammatory. The objective of this research was to examine the anti-neuroinflammatory effects and molecular mechanisms of an active fraction from SSD (ASSD) in vitro culture BV2 cells, a type of mouse microglia cell line. The inflammatory responses in BV2 cells were induced by stimulating them with 1 μg/mL lipopolysaccharide (LPS) and the effects of ASSD on LPS-stimulated inflammation were monitored. Besides, by using the methods of Western blot, immunofluorescence, and RT-PCR, the mechanisms of ASSD on microglia activation, M1/M2 polarization, and the TLR4/MyD88/NF-κB pathway were investigated. Our findings demonstrate that the treatment doses of ASSD neither induce cytotoxicity nor promote the production of inflammatory cytokines. In addition, immunofluorescence analysis show that ASSD inhibited the expression of ionized calcium-binding adapter molecule 1(Iba1) and inducible nitricoxide synthase (iNOS), and induced arginase 1 (Arg1) expression. Moreover, Western blot analysis indicated that ASSD significantly down-regulated TLR4, MyD88, p-IκB, NF-κB p65, and NF-κB p-p65 protein expression levels. Furthermore, RT-qPCR assay show that ASSD significantly down-regulated iNOS, TLR4, MyD88, and NF-κB mRNA expression levels, and up-regulated Arg1 mRNA expression level. According to the findings, ASSD can suppress microglia-mediated inflammatory responses by modulating microglia activation, inducing a shift from M1 to M2 polarization, and inhibiting the TLR4/MyD88/NF-κB signaling pathway.
Access this article: https://doi.org/10.1016/j.heliyon.2023.e14979
Title: Allogenic microglia replacement: A novel therapeutic strategy for neurological disorders
Authors: Yanxia Rao, BoPeng
Type: Review
Abstract:
Microglia are resident immune cells in the central nervous system (CNS) that play vital roles in CNS development, homeostasis and disease pathogenesis. Genetic defects in microglia lead to microglial dysfunction, which in turn leads to neurological disorders. The correction of the specific genetic defects in microglia in these disorders can lead to therapeutic effects. Traditional genetic defect correction approaches are dependent on viral vector-based genetic defect corrections. However, the viruses used in these approaches, including adeno-associated viruses, lentiviruses and retroviruses, do not primarily target microglia; therefore, viral vector-based genetic defect corrections are ineffective in microglia. Microglia replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy microglia. In this paper, we systematically review the history, rationale and therapeutic perspectives of microglia replacement, which would be a novel strategy for treating CNS disorders.
Access this article: https://doi.org/10.1016/j.fmre.2023.02.025
Title: A richer and more diverse future for microglia phenotypes
Authors: Jie Wang, Wenbin He, Junlong Zhang
Type: Review
Abstract:
Microglia are the only resident innate immune cells derived from the mesoderm in the nerve tissue. They play a role in the development and maturation of the central nervous system (CNS). Microglia mediate the repair of CNS injury and participate in endogenous immune response induced by various diseases by exerting neuroprotective or neurotoxic effects. Traditionally, microglia are considered to be in a resting state, the M0 type, under physiological conditions. In this state, they perform immune surveillance by constantly monitoring pathological responses in the CNS. In the pathological state, microglia undergo a series of morphological and functional changes from the M0 state and eventually polarize into classically activated microglia (M1) and alternatively activated microglia (M2). M1 microglia release inflammatory factors and toxic substances to inhibit pathogens, while M2 microglia exert neuroprotective effects by promoting nerve repair and regeneration. However, in recent years, the view regarding M1/M2 polarization of microglia has gradually changed. According to some researchers, the phenomenon of microglia polarization is not yet confirmed. The M1/M2 polarization term is used for a simplified description of its phenotype and function. Other researchers believe that the microglia polarization process is rich and diverse, and consequently, the classification method of M1/M2 has limitations. This conflict hinders the academic community from establishing more meaningful microglia polarization pathways and terms, and therefore, a careful revision of the concept of microglia polarization is required. The present article briefly reviews the current consensus and controversy regarding microglial polarization typing to provide supporting materials for a more objective understanding of the functional phenotype of microglia.
Access this article: https://doi.org/10.1016/j.heliyon.2023.e14713
Title: iPSC-sEVs alleviate microglia senescence to protect against ischemic stroke in aged mice
Authors: Xinyu Niu, Yuguo Xia, Lei Luo, Yu Chen, Ji Yuan, Juntao Zhang, Qing Li, Zhifeng Deng, Yang Wang
Type: Review
Abstract:
The polarization of microglia plays an important role in the outcome of ischemic stroke (IS). In the aged population, senescent microglia show a predominant pro-inflammatory phenotype, which leads to worse outcomes in aged ischemic stroke compared to young ischemic stroke. Recent research demonstrated that inducible pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) possess the significant anti-ageing ability. We hypothesized that iPSC-sEVs could alleviate microglia senescence to regulate microglia polarization in aged ischemic stroke. In this study, we showed that treatment with iPSC-sEVs significantly alleviated microglia senescence as indicated by the decreased senescence-associated proteins including P16, P21, P53, and γ-H2AX as well as the activity of SA-β-gal, and inhibited pro-inflammatory activation of microglia both in vivo and in vitro. Furthermore, iPSC-sEVs shifted microglia from pro-inflammatory phenotype to anti-inflammatory phenotype, which reduced the apoptosis of neurons, and improved the outcome of aged stroke mice. Mechanism studies showed that iPSC-sEVs reversed the loss of Rictor and downstream p-AKT (s473) in senescent microglia, which was involved in the senescence and pro-inflammatory phenotype regulation of microglia. Inhibition of Rictor abolished the iPSC-sEVs-afforded phosphorylation of AKT and alleviation of inflammation of senescent microglia. Proteomics results indicated that iPSC-sEVs carried transforming growth factor-β1 (TGF-β1) to upregulate Rictor and p-AKT in senescent microglia, which could be hindered by blocking TGF-β1. Taken together, our work demonstrates iPSC-sEVs reverse the senescent characteristic of microglia in aged brains and therefore improve the outcome after stroke, at least, via delivering TGF-β1 to upregulate Rictor and p-AKT. Our data suggest that iPSC-sEVs might be a novelty therapeutic method for aged ischemic stroke and other diseases involving senescent microglia.
Access this article: https://doi.org/10.1016/j.mtbio.2023.100600
