Sex‐specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury

Fiore, Nathan T.; Yin, Zhuoran; Güneykaya, Dilansu; Gauthier, Christian; Hayes, Jessica P.; A, D’Hary; Butovsky, Oleg; Moalem‐Taylor, Gila

doi:10.1002/glia.24133

Cited by 41 publications

(26 citation statements)

References 83 publications

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“…IFN-γ can also damage the CNS through microglia activation. In addition to activating resting microglia, stimulating the IFN-γR signaling pathway also upregulates the tyrosine kinase Lyn and purinergic P2X4 receptors of microglia, leading to abnormal neuronal excitation in dorsal horn neurons and neuropathic pain ( 45 ).…”

Section: Membrane Receptors and Pathways In Microglia Activationmentioning

confidence: 99%

Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

Qin

Chen

et al. 2023

Front. Neurol.

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Microglia are the principal resident immune cells in the central nervous system (CNS) and play important roles in the development of CNS disorders. In recent years, there have been significant developments in our understanding of microglia, and we now have greater insight into the temporal and spatial patterns of microglia activation in a variety of CNS disorders, as well as the interactions between microglia and neurons. A variety of signaling pathways have been implicated. However, to date, all published clinical trials have failed to demonstrate efficacy over placebo. This review summarizes the results of recent important studies and attempts to provide a mechanistic view of microglia activation, inflammation, tissue repair, and CNS disorders.

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Section: Membrane Receptors and Pathways In Microglia Activationmentioning

confidence: 99%

Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

Qin

Chen

et al. 2023

Front. Neurol.

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“…Microglia are frequently mixed, exhibiting both phenotypes. The idea of physiological state heterogeneity ( Li et al, 2019 ; Cadiz et al, 2022 ), and gender differences ( Fiore et al, 2022 ; Tansley et al, 2022 ; Ugidos et al, 2022 ) has slowly emerged in recent years, creating a new foundation for our complete understanding of microglia. At the same time, single-cell sequencing technology has also opened a new door for this ( Butovsky et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…Mainly including: 1. Microglial development ( Wurm et al, 2021 ; Iyer et al, 2022 ) and phenotypes in physiological or pathological conditions, also involving microglial heterogeneity in spatial and temporal ( Masuda et al, 2019 ), gender ( Dockman et al, 2022 ; Fiore et al, 2022 ), or other dimensions. 2.…”

Section: Discussionmentioning

confidence: 99%

Knowledge domains and emerging trends of microglia research from 2002 to 2021: A bibliometric analysis and visualization study

Liu

Yang

et al. 2023

Front. Aging Neurosci.

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BackgroundMicroglia have been identified for a century. In this period, their ontogeny and functions have come to light thanks to the tireless efforts of scientists. However, numerous documents are being produced, making it challenging for scholars, especially those new to the field, to understand them thoroughly. Therefore, having a reliable method for quickly grasping a field is crucial.MethodsWe searched and downloaded articles from the Web of Science Core Collection with “microglia” or “microglial” in the title from 2002 to 2021. Eventually, 12,813 articles were located and, using CiteSpace and VOSviewer, the fundamental data, knowledge domains, hot spots, and emerging trends, as well as the influential literature in the field of microglia research, were analyzed.ResultsFollowing 2011, microglia publications grew significantly. The two prominent journals are Glia and J Neuroinflamm. The United States and Germany dominated the microglia study. The primary research institutions are Harvard Univ and Univ Freiburg, and the leading authors are Prinz Marco and Kettenmann Helmut. The knowledge domains of microglia include eight directions, namely neuroinflammation, lipopolysaccharide, aging, neuropathic pain, macrophages, Alzheimer’s disease, retina, and apoptosis. Microglial phenotype is the focus of research; while RNA-seq, exosome, and glycolysis are emerging topics, a microglial-specific marker is still a hard stone. We also identified 19 influential articles that contributed to the study of microglial origin (Mildner A 2007; Ginhoux F 2010), identity (Butovsky O 2014), homeostasis (Cardona AE 2006; Elmore MRP 2014); microglial function such as surveillance (Nimmerjahn A 2005), movement (Davalos D 2005; Haynes SE 2006), phagocytosis (Simard AR 2006), and synapse pruning (Wake H 2009; Paolicelli RC 2011; Schafer DP 2012; Parkhurst CN 2013); and microglial state/phenotype associated with disease (Keren-Shaul H 2017), as well as 5 review articles represented by Kettenmann H 2011.ConclusionUsing bibliometrics, we have investigated the fundamental data, knowledge structure, and dynamic evolution of microglia research over the previous 20 years. We hope this study can provide some inspiration and a reference for researchers studying microglia in neuroscience.

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“…The mechanical pain hypersensitivity test was conducted on the rats of both groups using von Frey fibres [3] at the D0, D3, and D7 timepoints after BND surgery. The rats were acclimated to the testing apparatus for at least 30 min before behavioural testing.…”

Section: Mechanical Pain Hypersensitivity Testmentioning

confidence: 99%

“…Microglia are immune cells that constantly maintain the microenvironment and homeostasis of the central nervous system (CNS) [2][3][4]. Several studies have confirmed the crucial role of microglia in neuropathic pain [3,4].…”

Section: Introductionmentioning

confidence: 99%

The temporal and spatial signature of microglial transcriptome in neuropathic pain

Liu

Dai

et al. 2023

NeuroReport

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Microglial activation following peripheral nerve injury is crucial for neuropathic pain (NP) development; however, studies on time-specific and spatial characteristics of microglial transcriptome are scarce. Firstly, we comparatively analysed microglial transcriptome of different brain regions and multiple timepoints after nerve injury by analysing the gene expression profile of GSE180627 and GSE117320. Then, we performed a mechanical pain hypersensitivity test on 12 rat neuropathic pain models using von Frey fibres at various timepoints after nerve injury. To further explore the key gene clusters closely related to the neuropathic pain phenotype, we conducted a weighted gene co-expression network analysis (WGCNA) on the GSE60670 gene expression profile. Lastly, we performed a single-cell sequencing analysis on GSE162807 for identifying microglia subpopulations. We found that the trend of microglia's transcriptome changes after nerve injury was that mRNA expression changes mainly occur early after injury, which is also consistent with phenotypic changes (NP progression). We also revealed that in addition to spatial specificity, microglia are also temporally specific in NP progression following nerve injury. The WGCNA findings revealed that the functional analysis of the key module genes emphasized the endoplasmic reticulum's (ER's) crucial role in NP. In our single-cell sequencing analysis, microglia were clustered into 18 cell subsets, of which we identified specific subsets of two timepoints (D3/D7) post-injury. Our study further revealed the temporal and spatial gene expression specificity of microglia in neuropathic pain. These results contribute to our comprehensive understanding of the pathogenic mechanism of microglia in neuropathic pain.

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Sex‐specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury

Cited by 41 publications

References 83 publications

Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

Knowledge domains and emerging trends of microglia research from 2002 to 2021: A bibliometric analysis and visualization study

The temporal and spatial signature of microglial transcriptome in neuropathic pain

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