Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review DOI Creative Commons
Shalini Dhir,

Hannah Derue,

Alfredo Ribeiro‐da‐Silva

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 6, 2024

Neuropathic pain (NP) is an ineffectively treated, debilitating chronic disorder that associated with maladaptive changes in the central nervous system, particularly spinal cord. Murine models of NP looking at mechanisms underlying these suggest important role microglia, resident immune cells various stages disease progression. However, given number different and resource limitations come tracking longitudinal animals, many studies fail to truly recapitulate patterns exist between conditions temporal microglial changes. This review integrates how are being carried out murine microglia over time can affect behavior order inform better study design highlight knowledge gaps field. 258 peer-reviewed, primary source articles were selected using Covidence. Trends type mice, statistical tests, models, interventions, markers recorded analyzed. Studies primarily conducted inbred, young adult, male mice having peripheral nerve injury which highlights lack generalizability data currently collected. Changes behavior, both increased, tested most commonly up 2 weeks after initiation despite aberrant activity also later points conditions. treatments decrease show decreased 1- 2-week point not recording involvement dysfunction their development. These results need for only studying dynamics a variety longer but clinically relevant considerations.

Language: Английский

Sex differences in mechanisms of pain hypersensitivity DOI Creative Commons
Jeffrey S. Mogil, Marc Parisien,

Sahel Jahangiri Esfahani

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 163, P. 105749 - 105749

Published: June 3, 2024

The introduction of sex-as-a-biological-variable policies at funding agencies around the world has led to an explosion very recent observations sex differences in biology underlying pain. This review considers evidence sexually dimorphic mechanisms mediating pain hypersensitivity, derived from modern assays persistent rodent animal models. Three well-studied findings are described detail: male-specific role spinal cord microglia, female-specific calcitonin gene-related peptide (CGRP), and prolactin its receptor. Other sex-specific molecular involvement subjected pathway analyses reveal least one novel hypothesis: that females may preferentially use Th1 males Th2 T cell activity mediate chronic

Language: Английский

Citations

19
Ai-Driven Discovery of Brain-Penetrant Galectin-3 Inhibitors for Alzheimer's Disease Therapy DOI
Zu‐Cheng Ye, Xueyan Liu,

Jiexin Xu

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

1
TET1 participates in oxaliplatin-induced neuropathic pain by regulating microRNA-30b/Nav1.6 DOI Creative Commons
Sen Zhao, Jingjing Zhang, Mengya Zhang

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108228 - 108228

Published: Jan. 1, 2025

Chemotherapy-induced neuropathic pain poses significant clinical challenges and severely impacts patient quality of life. Sodium ion channels are crucial in regulating neuronal excitability pain. Our research indicates that the microRNA-30b (miR-30b) rat dorsal root ganglia (DRG) contributes to chemotherapy-induced by Nav1.6 protein. Additionally, Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) plays a role generation altering gene expression. We established neuropathy model using intraperitoneal Oxaliplatin (OXA) injections measured TET1 protein DRG. Using lentivirus Tet1flox/flox mice, we modulated expression assessed behaviors, DRG excitability, currents, miR-30b-5p, demethylation Mir30b promoter region. employed Chromatin immunoprecipitation (CHIP) pinpoint binding sites on promoter. The miR-30b agomir or antagomir responses were post-intrathecal injections. results showed OXA reduced TET1, increasing miR-30b-5p knockdown exacerbated these effects induced behaviors. Conversely, overexpression reversed effects. also targeted enhanced at (-1103 bp -1079 bp). reduces Nav1.6, whereas reverses TET1's In OXA-induced neuropathy, decreased miR-30b, elevating contributing hypothesize mediates this process

Language: Английский

Citations

0
Perturbations in the microbiota-gut-brain axis shaped by social status loss DOI Creative Commons

Ruijing Yang,

Xin Wang,

Jie Yang

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 8, 2025

Abstract Social status is closely linked to physiological and psychological states. Loss of social dominance can lead brain disorders such as depression, but the underlying mechanisms remain unclear. The gut microbiota sense stress contribute via microbiota-gut-brain axis (MGBA). Here, using a forced loss paradigm demote dominant mice subordinate ranks, we find that alters composition function microbiota, increasing Muribaculaceae abundance enhancing butanoate metabolism, microbial depletion resists loss-induced hierarchical demotion behavioral alteration. Single-nucleus transcriptomic analysis prefrontal cortex (PFC) indicates primarily affected interneurons, altering GABAergic synaptic transmission. Weighted gene co-expression network (WGCNA) reveals modules in colon, PFC, PFC suggesting changes PI3K-Akt signaling pathway glutamatergic synapse. Our findings provide evidence for MGBA perturbations induced by loss, offering potential intervention targets related disorders.

Language: Английский

Citations

0
How microglia contribute to the induction and maintenance of neuropathic pain DOI
Marzia Malcangio, George Sideris-Lampretsas

Nature reviews. Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

Citations

0
TLR9 in satellite glial cells promotes paclitaxel-induced neuropathic pain by reducing Kir4.1 transcription through histone methylation activation DOI
Qingtian Luo, Jian Jiang,

Qing Zhu

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Analgesic Mechanism of Emodin in Neuropathic Pain Through Inhibiting P2X4 Purinoceptor Signaling DOI
Peng Chen,

Qian Gong,

Hao Wang

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

0
Cannabinoid CB2 receptor controls chronic itch by regulating spinal microglial activation and synaptic transmission DOI Creative Commons
Kangtai Xu, Xuefei Liu, Qian Zeng

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115559 - 115559

Published: April 1, 2025

Chronic itch is a devastating clinical condition, and its central mechanisms remain poorly understood. We reported that spinal cannabinoid receptor type 2 (CB2R) activation exerts antipruritic effects escalates in mice lacking Cnr2 mouse models of dermatitis psoriasis. In the cord, CB2R mainly expressed microglia, microglial ablation or inhibition attenuated chronic itch, suggesting contributes to itch. Particularly, conditional deletion microglia also exacerbated mice. Single-cell RNA sequencing molecular mechanistic studies suggest reprogrammed by inducing anti-inflammatory suppressor cytokine signaling 3 (SOCS3) reducing itch-related p38 signal transducer activator transcription 1 (STAT1) phosphorylation. Finally, suppressed neuronal excitability synaptic transmission gastrin-releasing peptide (GRP)/GRP (GRPR) interneurons ascending projection neurons inhibiting microglia-derived cytokines. These findings demonstrate while alleviates via neuro-immune interactions.

Language: Английский

Citations

0
Hspb1 and Lgals3 in spinal neurons are closely associated with autophagy following excitotoxicity based on machine learning algorithms DOI Creative Commons
Lei Yan, Zihao Li, Chuanbo Li

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0303235 - e0303235

Published: May 10, 2024

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, specific mechanism underlying relationship between excitotoxicity SCI has been largely overlooked. In this study, we isolated neurons from neonatal rats induced excitotoxic by high concentrations glutamic acid, mimicking an model. Subsequently, performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest (RF), least absolute shrinkage selection operator (LASSO), conducted comprehensive investigation into key genes associated with neuron injury. We also utilized protein-protein interaction (PPI) to identify pivotal proteins regulating gene expression analyzed public datasets (GSE2599, GSE20907, GSE45006, GSE174549). Our findings revealed that six genes—Anxa2, S100a10, Ccng1, Timp1, Hspb1, Lgals3—were significantly upregulated not only vitro subjected but subacute SCI. Furthermore, Hspb1 Lgals3 were closely linked excitotoxicity. contribute better understanding autophagy, offering potential targets theoretical foundation for diagnosis treatment.

Language: Английский

Citations

3
Implications of TRPM3 and TRPM8 for sensory neuron sensitisation DOI
Marc Behrendt

Biological Chemistry, Journal Year: 2024, Volume and Issue: 405(9-10), P. 583 - 599

Published: Sept. 30, 2024

Abstract Sensory neurons serve to receive and transmit a wide range of information about the conditions world around us as well external internal state our body. Sensitisation these nerve cells, i.e. becoming more sensitive stimuli or emergence intensification spontaneous activity, for example in context inflammation injury, can lead chronic diseases such neuropathic pain. For many disorders there are only very limited treatment options order find establish new therapeutic approaches, research into exact causes sensitisation with elucidation underlying mechanisms identification molecular components is therefore essential. These include plasma membrane receptors ion channels that involved signal reception transmission. Members transient receptor potential (TRP) channel family also expressed sensory some them play crucial role temperature perception. This review article focuses on heat-sensitive TRPM3 cold-sensitive TRPM8 (and TRPA1) their importance dorsal root ganglion discussed based studies related injury- chemotherapy-induced neuropathy.

Language: Английский

Citations

3