Local substitution of GDF-15 improves axonal and sensory recovery after peripheral nerve injury

Mensching, Leonore; Börger, Ann-Kathrin; Wang, Xialong; Charalambous, Petar; Unsicker, Klaus; Haastert‐Talini, Kirsten

doi:10.1007/s00441-012-1493-6

Cited by 29 publications

(19 citation statements)

References 40 publications

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“…GDF15 is expressed in both the CNS and the peripheral nervous system (PNS) (22). Although the precise biological function of GDF15 in the nervous system, including the retina, remain poorly understood, previous literature demonstrated its neurotrophic or neuroprotective effect in CNS (22) and PNS (23,24). In addition, GDF15 has previously been demonstrated to Values are mean ± SD.…”

Section: Discussionmentioning

confidence: 99%

GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

Ban¹,

Siegfried²,

Lin³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

Ban¹,

Siegfried²,

Lin³

et al. 2017

JCI Insight

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“…A report from Strelau et al [8] showed that GDF15-deficient mice exhibit progressive postnatal losses of spinal, facial and trigeminal motoneurons, as well as sensory neurons in the dorsal root ganglia. Recently, one study suggested that GDF15 was a potential support factor for neuronal synaptic development and integration during axonal elongation [9]. Although these data suggest that GDF15 plays a critical role in the central nervous system, the signal transduction pathways and the receptor subtypes involved are not well understand.…”

Section: Introductionmentioning

confidence: 99%

GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells

Wang

Huang

Zhou

et al. 2014

Biochemical Journal

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GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.

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“…After crush injury of the sciatic nerve, motor function of the lower limb is assessed by the static sciatic index (SSI) for sciatic function. 1 Several studies have examined sciatic nerve crush injuries and functional assessments using the SSI; 15,17,18 however, it remains unclear which sciatic nerve component (tibial or common peroneal nerve) exerts a marked influence on lower limb motor function assessed by the SSI. We first examined the effect of resection of either the tibial or common peroneal nerve on motor function in rats, and then investigated to what extent undamaged residual axons contributed to preserving motor function in rats that had undergone varying degrees of nerve crush injuries.…”

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confidence: 99%

Effect of graded nerve pressure injuries on motor function

Karasawa¹,

Yokouchi²,

Kakegawa³

et al. 2015

JNS

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Methods animalsThe experiments were performed on 42 adult female Wistar rats (180-220 g body weight; Japan SLC Inc.). All procedures were conducted in accordance with the NIH abbreviatioN SSI = static sciatic index. subMitted June 27, 2014. accepted September 11, 2014. iNclude wheN citiNg Published online March 6, 2015; DOI: 10.3171/2014.9.JNS141451. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Effect of graded nerve pressure injuries on motor functionMika Karasawa, MM, Kumiko yokouchi, phd, akira Kakegawa, phd, Kyutaro Kawagishi, Md, phd, tetsuji Moriizumi, Md, phd, and Nanae Fukushima, Md, phd Department of Anatomy, Shinshu University School of Medicine, Matsumoto, Japan obJect The purpose of this study was to determine the minimum amount of nerve fibers required to maintain normal motor function after nerve injury in rats. Methods The authors first confirmed that a common peroneal nerve injury caused more aggravating effects on lower limb motor function than tibial nerve injury, as assessed by the static sciatic index (SSI). Thereafter, rats were subjected to varying degrees of crush injury to the common peroneal nerve. At 48 hours after the injury, motor function was assessed using the SSI and slope-walking ability (with slope angles of 30° and 45°). The tibialis anterior muscle, a main muscle innervated by the common peroneal nerve, was removed. Muscle sections were co-labeled with neuronal class III b-tubulin polyclonal antibody to identify the presence of axons and Alexa Fluor 488-conjugated a-bungarotoxin to identify the presence of motor endplates. results The evaluation of neuromuscular innervation showed a correlation between SSI scores and ratios of residual axons (r s = 0.68, p < 0.01), and there was a statistically significant difference between slope-walking ability and ratios of residual axons (p < 0.01). Moreover, the ratios of residual axons in the nerve-crushed rats with normal motor function (SSI above -20) ranged from 36.5% to 88.7%, and those ratios in the success group with slope-walking angles of 30° and 45° ranged from 14.7% to 88.7% and from 39.8% to 88.7%, respectively. coNclusioNs In this study of rodents, less than half of the motor axons were sufficient to maintain normal motor function of the lower limb.

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Local substitution of GDF-15 improves axonal and sensory recovery after peripheral nerve injury

Cited by 29 publications

References 40 publications

GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells

Effect of graded nerve pressure injuries on motor function

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