Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord

Xu, Yunlong; Jiang, Yanjun; Wang, Lin; Huang, Jiahua; Wen, Junping; Lv, Hang; Wu, Xiaoli; Wan, Chaofan; Yu, Chuan-xin; Zhang, Wenjie; Zhao, Jiaying; Zhou, Yinqi; Chen, Yongjun

doi:10.1007/s12264-019-00346-z

Cited by 24 publications

(17 citation statements)

References 77 publications

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“…Mechanical sensitivity. The tactile sensitivity of the hindlimb was assessed in a subset of the animals (yap f/f male mice, yap GFAP -CKO male mice, bFGF-treated and XMU-MP-1-treated WT male mice) using von Frey hair (Faw et al, 2018;Xu et al, 2019). Briefly, the mice were placed under a small, opaque container on an elevated wire mesh to allow access to the plantar surface of the paws.…”

Section: Methodsmentioning

confidence: 99%

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury

Xie

Shen

et al. 2020

J. Neurosci.

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Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27 Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27 Kip1 pathway positively regulates astrocytic proliferation after SCI.

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Section: Methodsmentioning

confidence: 99%

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury

Xie

Shen

et al. 2020

J. Neurosci.

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“…Recent studies have shown that spinal cord dysfunction may be one of the underlying pathogenesis of IBS (Zhao et al, 2017 ; Qi et al, 2019 ; Fan et al, 2020 ). As a primary center, the spinal cord plays an important role in the regulation of pain perception (Braz et al, 2014 ; Ji et al, 2019 ; Xu et al, 2019 ). However, the regulation of visceral pain sensitivity at the spinal cord level is rarely reported, so the mechanism remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Spinal ASIC1 and NKCC1 Expression Contributes to Chronic Visceral Pain in Rats

Tian

et al. 2021

Front. Mol. Neurosci.

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Aims: To determine whether acid-sensing ion channel 1 (ASIC1)–sodium-potassium-chloride cotransporter 1 (NKCC1) signaling pathway participates in chronic visceral pain of adult rats with neonatal maternal deprivation (NMD).Methods: Chronic visceral pain was detected by colorectal distension (CRD). Western blotting and Immunofluorescence were performed to detect the expression and location of ASIC1 and NKCC1. Whole-cell patch-clamp recordings were performed to record spinal synaptic transmission.Results: The excitatory synaptic transmission was enhanced and the inhibitory synaptic transmission was weakened in the spinal dorsal horn of NMD rats. ASIC1 and NKCC1 protein expression in the spinal dorsal horn was significantly up-regulated in NMD rats. Incubation of Amiloride reduced the amplitude of mEPSCs. Incubation of Bumetanide (BMT) increased the amplitude of mIPSCs. Intrathecal injection of ASIC1 or NKCC1 inhibitors reversed the threshold of CRD in NMD rats. Also, Amiloride treatment significantly reversed the expression of NKCC1 in the spinal dorsal horn of NMD rats.Conclusion: Our data suggest that the ASIC1-NKCC1 signaling pathway is involved in chronic visceral pain in NMD rats.

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“…The spinal cord is the first relay area of sensory information from the periphery to the center. It plays a regulatory role in transmitting and integrating pain information 11‐13 . It is, therefore, necessary to explore the role of spinal dorsal horn in enterodynia.…”

Section: Introductionmentioning

confidence: 99%

“…It plays a regulatory role in transmitting and integrating pain information. [11][12][13] It is, therefore, necessary to explore the role of spinal dorsal horn in enterodynia.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of spinal ASIC1 by miR‐485 mediates enterodynia in adult offspring rats with prenatal maternal stress

Xue

et al. 2020

CNS Neurosci Ther

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Aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease characterized by abdominal pain. Our recent study has shown that the acid‐sensitive ion channel 1 (ASIC1) in dorsal root ganglion (DRG) is involved in stomachache of adult offspring rats subjected with prenatal maternal stress (PMS). MiR‐485 is predicted to target the expression of ASIC1. The aim of the present study was designed to determine whether miR‐485/ASIC1 signaling participates in enterodynia in the spinal dorsal horn of adult offspring rats with PMS. Methods Enterodynia was measured by colorectal distension (CRD). Western blotting, qPCR, and in situ hybridization were performed to detect the expression of ASICs and related miRNAs. Spinal synaptic transmission was also recorded by patch clamping. Results PMS offspring rats showed that spinal ASIC1 protein expression and synaptic transmission were significantly enhanced. Administration of ASICs antagonist amiloride suppressed the synaptic transmission and enterodynia. Besides, PMS induced a significant reduction in the expression of miR‐485. Upregulating the expression markedly attenuated enterodynia, reversed the increase in ASIC1 protein and synaptic transmission. Furthermore, ASIC1 and miR‐485 were co‐expressed in NeuN‐positive spinal dorsal horn neurons. Conclusions Overall, these data suggested that miR‐485 participated in enterodynia in PMS offspring, which is likely mediated by the enhanced ASIC1 activities.

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Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord

Cited by 24 publications

References 77 publications

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury

Upregulation of Spinal ASIC1 and NKCC1 Expression Contributes to Chronic Visceral Pain in Rats

Upregulation of spinal ASIC1 by miR‐485 mediates enterodynia in adult offspring rats with prenatal maternal stress

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