The Silencing of Iba-1 Changes the Physiology of Microglia

Deftu, Alexandru‐Florian; Filippi, Alexandru; Gheorghe, Roxana; Chirițoiu, Gabriela; Grosu, Andreea; Floare, Mara; Tuchilus, Angelica; Ristoiu, Violeta

doi:10.37897/rjn.2017.s2.4

Cited by 2 publications

(2 citation statements)

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“…Particularly, CXCL1, which is also secreted by both SC and macrophages, has been associated with physical inhibition of axonal outgrowth in DRG neuron (Deftu et al, 2019). CXCL1 interferes with the functioning of TRPV1 (Transient Receptor Potential 1) receptors in TRPV1 + /IB4 (Isolectin B4) + DRG neurons (Deftu et al, 2017). These effects are important as studies have shown that TRPV1 receptors are physically and functionally present at dynamic neuronal extensions, including growth cones of embryonic and adult DRG neurons (Goswami et al, 2007).…”

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confidence: 99%

Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury

Fuentes‐Flores,

Geronimo‐Olvera,

Girardi

et al. 2023

EMBO Mol Med

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Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c‐Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and following chronic denervation, which can lead to poor clinical outcomes. While diminished c‐Jun expression in SCs has been associated with regenerative failure, it is unclear whether the inability to maintain a repair state is associated with the transition into an axonal growth inhibition phenotype. We here find that reparative SCs transition into a senescent phenotype, characterized by diminished c‐Jun expression and secretion of inhibitory factors for axonal regeneration in aging and chronic denervation. In both conditions, the elimination of senescent SCs by systemic senolytic drug treatment or genetic targeting improved nerve regeneration and functional recovery, increased c‐Jun expression and decreased nerve inflammation. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration and functional recovery after peripheral nerve injuries.

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confidence: 99%

Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury

Fuentes‐Flores,

Geronimo‐Olvera,

Girardi

et al. 2023

EMBO Mol Med

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“…Moreover, the CXCL1 pathway in DRG neurons triggers neutrophil recruitment and subsequent mechanical allodynia (Zhang et al, 2019). Most importantly, a previous study demonstrated that short-term application of CXCL1 is able to modulate the activity of TRPV1+/IB4+ DRG neurons (Deftu et al, 2017(Deftu et al, , 2018. In addition, PKCε activation in IB4+ DRG neurons and increased TRPV1 expression play an important role in pain transition (Wang et al, 2018;Fang et al, 2021).…”

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confidence: 97%

Satellite glial cells drive the transition from acute to chronic pain in a rat model of hyperalgesic priming

Yi²,

Xi³

et al. 2023

Front. Mol. Neurosci.

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Chronic pain is one of the most common clinical syndromes affecting patients’ quality of life. Regulating the transition from acute to chronic pain is a novel therapeutic strategy for chronic pain that presents a major clinical challenge. However, the mechanism underlying pain transitions remains poorly understood. A rat hyperalgesic priming (HP) model, which mimics pain transition, was established decades ago. Here, this HP model and RNA sequencing (RNA-seq) were used to study the potential role of neuroinflammation in pain transition. In this study, HP model rats developed prolonged hyperalgesia in the hind paw after carrageenan (Car) and PGE2 injection, accompanied by obvious satellite glial cell (SGC) activation in the dorsal root ganglion (DRG), as indicated by upregulation of GFAP. RNA-Seq identified a total of differentially expressed genes in the ipsilateral DRG in HP model rats. The expression of several representative genes was confirmed by real-time quantitative PCR (qPCR). Functional analysis of the differentially expressed genes indicated that genes related to the inflammatory and neuroinflammatory response showed the most significant changes in expression. We further found that the expression of the chemokine CXCL1 was significantly upregulated in the rat DRG. Pharmacological blockade of CXCL1 reduced protein kinase C epsilon overproduction as well as hyperalgesia in HP rats but did not prevent the upregulation of GFAP in the DRG. These results reveal that neuroinflammatory responses are involved in pain transition and may be the source of chronic pain. The chemokine CXCL1 in the DRG is a pivotal contributor to chronic pain and pain transition in HP model rats. Thus, our study provides a putative novel target for the development of effective therapeutics to prevent pain transition.

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The Silencing of Iba-1 Changes the Physiology of Microglia

Cited by 2 publications

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Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury

Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury

Satellite glial cells drive the transition from acute to chronic pain in a rat model of hyperalgesic priming

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