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Erschienen in: Journal of Neurology 11/2019

07.08.2019 | Original Communication

Reduced gene expression of netrin family members in skin and sural nerve specimens of patients with painful peripheral neuropathies

verfasst von: Anna-Lena Schubert, Melissa Held, Claudia Sommer, Nurcan Üçeyler

Erschienen in: Journal of Neurology | Ausgabe 11/2019

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Abstract

Objective

To investigate the expression of axon guidance cues in skin and sural nerve biopsies of patients with polyneuropathies (PNP) as potential markers of nerve de- and regeneration and inflammation.

Methods

We prospectively recruited 88 patients with PNP and compared data between patient subgroups and healthy controls. All patients underwent skin punch and/or sural nerve biopsy at the lower leg and proximal thigh. We characterized gene expression profiles of netrin family members as target genes involved in neuronal de- and regeneration [netrin 1, deleted in colorectal cancer (DCC), uncoordinated5H2, neogenin 1 (NEO1), netrin G1, netrin G2] using quantitative real-time PCR.

Results

Gene expression of netrin 1 (p < 0.05 in proximal skin), DCC (p < 0.001 in distal skin), NEO1 (p < 0.05 in distal skin), netrin G1 (p < 0.05 in proximal and p < 0.01 in distal skin), and netrin G2 (p < 0.001 in distal skin) was lower in skin biopsies of patients with neuropathy compared to healthy controls. Gene expression of NEO1 (p < 0.05 in distal skin), netrin G2 (p < 0.05 in distal skin), and DCC (p < 0.05 in sural nerve) was lower in samples of patients with painful compared to painless PNP and also correlated positively with intraepidermal nerve fiber density. Skin and sural nerve gene expression of the investigated target genes did not differ between neuropathies of different etiologies.

Conclusion

We show reduced cutaneous and neural axon guide expression, which may contribute to a dysregulation of nerve fiber de- and regeneration.
Literatur
1.
Zurück zum Zitat Dickson BJ (2002) Molecular mechanisms of axon guidance. Science 298:1959–1964PubMed Dickson BJ (2002) Molecular mechanisms of axon guidance. Science 298:1959–1964PubMed
3.
Zurück zum Zitat Round J, Stein E (2007) Netrin signaling leading to directed growth cone steering. Curr Opin Neurobiol 17:15–21PubMed Round J, Stein E (2007) Netrin signaling leading to directed growth cone steering. Curr Opin Neurobiol 17:15–21PubMed
4.
Zurück zum Zitat Cirulli V, Yebra M (2007) Netrins: beyond the brain. Nat Rev Mol Cell Biol 8:296–306PubMed Cirulli V, Yebra M (2007) Netrins: beyond the brain. Nat Rev Mol Cell Biol 8:296–306PubMed
5.
Zurück zum Zitat Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, Tessier-Lavigne M (1996) Deleted in colorectal cancer (DCC) encodes a netrin receptor. Cell 87:175–185 Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, Tessier-Lavigne M (1996) Deleted in colorectal cancer (DCC) encodes a netrin receptor. Cell 87:175–185
6.
Zurück zum Zitat Xu K, Wu Z, Renier N, Antipenko A, Tzvetkova-Robev D, Xu Y, Minchenko M, Nardi-Dei V, Rajashankar KR, Himanen J, Tessier-Lavigne M, Nikolov DB (2014) Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism. Science 344:1275–1279PubMedPubMedCentral Xu K, Wu Z, Renier N, Antipenko A, Tzvetkova-Robev D, Xu Y, Minchenko M, Nardi-Dei V, Rajashankar KR, Himanen J, Tessier-Lavigne M, Nikolov DB (2014) Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism. Science 344:1275–1279PubMedPubMedCentral
7.
Zurück zum Zitat Ackerman SL, Kozak LP, Przyborski SA, Rund LA, Boyer BB, Knowles BB (1997) The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein. Nature 386:838–842PubMed Ackerman SL, Kozak LP, Przyborski SA, Rund LA, Boyer BB, Knowles BB (1997) The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein. Nature 386:838–842PubMed
8.
Zurück zum Zitat Hong K, Hinck L, Nishiyama M, Poo MM, Tessier-Lavigne M, Stein E (1999) A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97:927–941 Hong K, Hinck L, Nishiyama M, Poo MM, Tessier-Lavigne M, Stein E (1999) A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97:927–941
9.
Zurück zum Zitat Nakashiba T, Ikeda T, Nishimura S, Tashiro K, Honjo T, Culotti JG, Itohara S (2000) Netrin-G1: a novel glycosyl phosphatidylinositol-linked mammalian netrin that is functionally divergent from classical netrins. J Neurosci 20:6540–6550PubMedPubMedCentral Nakashiba T, Ikeda T, Nishimura S, Tashiro K, Honjo T, Culotti JG, Itohara S (2000) Netrin-G1: a novel glycosyl phosphatidylinositol-linked mammalian netrin that is functionally divergent from classical netrins. J Neurosci 20:6540–6550PubMedPubMedCentral
10.
Zurück zum Zitat Nakashiba T, Nishimura S, Ikeda T, Itohara S (2002) Complementary expression and neurite outgrowth activity of netrin-G subfamily members. Mech Dev 111:47–60PubMed Nakashiba T, Nishimura S, Ikeda T, Itohara S (2002) Complementary expression and neurite outgrowth activity of netrin-G subfamily members. Mech Dev 111:47–60PubMed
11.
Zurück zum Zitat Niimi K, Nishimura-Akiyoshi S, Nakashiba T, Itohara S (2007) Monoclonal antibodies discriminating netrin-G1 and netrin-G2 neuronal pathways. J Neuroimmunol 192:99–104PubMed Niimi K, Nishimura-Akiyoshi S, Nakashiba T, Itohara S (2007) Monoclonal antibodies discriminating netrin-G1 and netrin-G2 neuronal pathways. J Neuroimmunol 192:99–104PubMed
12.
Zurück zum Zitat Lin JC, Ho WH, Gurney A, Rosenthal A (2003) The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat Neurosci 6:1270–1276PubMed Lin JC, Ho WH, Gurney A, Rosenthal A (2003) The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat Neurosci 6:1270–1276PubMed
13.
Zurück zum Zitat Matsukawa H, Akiyoshi-Nishimura S, Zhang Q, Lujan R, Yamaguchi K, Goto H, Yaguchi K, Hashikawa T, Sano C, Shigemoto R, Nakashiba T, Itohara S (2014) Netrin-G/NGL complexes encode functional synaptic diversification. J Neurosci 34:15779–15792PubMedPubMedCentral Matsukawa H, Akiyoshi-Nishimura S, Zhang Q, Lujan R, Yamaguchi K, Goto H, Yaguchi K, Hashikawa T, Sano C, Shigemoto R, Nakashiba T, Itohara S (2014) Netrin-G/NGL complexes encode functional synaptic diversification. J Neurosci 34:15779–15792PubMedPubMedCentral
14.
Zurück zum Zitat Mulero P, Cordova C, Hernandez M, Martin R, Gutierrez B, Munoz JC, Redondo N, Gallardo I, Tellez N, Nieto ML (2017) Netrin-1 and multiple sclerosis: a new biomarker for neuroinflammation? Eur J Neurol 24:1108–1115PubMed Mulero P, Cordova C, Hernandez M, Martin R, Gutierrez B, Munoz JC, Redondo N, Gallardo I, Tellez N, Nieto ML (2017) Netrin-1 and multiple sclerosis: a new biomarker for neuroinflammation? Eur J Neurol 24:1108–1115PubMed
15.
Zurück zum Zitat Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan WM, Peeva M, Servattalab S, Lam AN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich AJ, Robson CD, Grant PE, Bosley TM, Engle EC, Walsh CA, Yu TW (2017) Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet 49:606–612PubMedPubMedCentral Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan WM, Peeva M, Servattalab S, Lam AN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich AJ, Robson CD, Grant PE, Bosley TM, Engle EC, Walsh CA, Yu TW (2017) Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet 49:606–612PubMedPubMedCentral
16.
Zurück zum Zitat Marsh AP, Heron D, Edwards TJ, Quartier A, Galea C, Nava C, Rastetter A, Moutard ML, Anderson V, Bitoun P, Bunt J, Faudet A, Garel C, Gillies G, Gobius I, Guegan J, Heide S, Keren B, Lesne F, Lukic V, Mandelstam SA, McGillivray G, McIlroy A, Meneret A, Mignot C, Morcom LR, Odent S, Paolino A, Pope K, Riant F, Robinson GA, Spencer-Smith M, Srour M, Stephenson SE, Tankard R, Trouillard O, Welniarz Q, Wood A, Brice A, Rouleau G, Attie-Bitach T, Delatycki MB, Mandel JL, Amor DJ, Roze E, Piton A, Bahlo M, Billette de Villemeur T, Sherr EH, Leventer RJ, Richards LJ, Lockhart PJ, Depienne C (2017) Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. Nat Genet 49:511–514PubMedPubMedCentral Marsh AP, Heron D, Edwards TJ, Quartier A, Galea C, Nava C, Rastetter A, Moutard ML, Anderson V, Bitoun P, Bunt J, Faudet A, Garel C, Gillies G, Gobius I, Guegan J, Heide S, Keren B, Lesne F, Lukic V, Mandelstam SA, McGillivray G, McIlroy A, Meneret A, Mignot C, Morcom LR, Odent S, Paolino A, Pope K, Riant F, Robinson GA, Spencer-Smith M, Srour M, Stephenson SE, Tankard R, Trouillard O, Welniarz Q, Wood A, Brice A, Rouleau G, Attie-Bitach T, Delatycki MB, Mandel JL, Amor DJ, Roze E, Piton A, Bahlo M, Billette de Villemeur T, Sherr EH, Leventer RJ, Richards LJ, Lockhart PJ, Depienne C (2017) Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. Nat Genet 49:511–514PubMedPubMedCentral
17.
Zurück zum Zitat Madison RD, Zomorodi A, Robinson GA (2000) Netrin-1 and peripheral nerve regeneration in the adult rat. Exp Neurol 161:563–570PubMed Madison RD, Zomorodi A, Robinson GA (2000) Netrin-1 and peripheral nerve regeneration in the adult rat. Exp Neurol 161:563–570PubMed
18.
Zurück zum Zitat Webber CA, Christie KJ, Cheng C, Martinez JA, Singh B, Singh V, Thomas D, Zochodne DW (2011) Schwann cells direct peripheral nerve regeneration through the netrin-1 receptors, DCC and Unc5H2. Glia 59:1503–1517PubMed Webber CA, Christie KJ, Cheng C, Martinez JA, Singh B, Singh V, Thomas D, Zochodne DW (2011) Schwann cells direct peripheral nerve regeneration through the netrin-1 receptors, DCC and Unc5H2. Glia 59:1503–1517PubMed
19.
Zurück zum Zitat Lv J, Sun X, Ma J, Ma X, Zhang Y, Li F, Li Y, Zhao Z (2015) Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor. Biochem Biophys Res Commun 464:263–268PubMed Lv J, Sun X, Ma J, Ma X, Zhang Y, Li F, Li Y, Zhao Z (2015) Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor. Biochem Biophys Res Commun 464:263–268PubMed
20.
Zurück zum Zitat Berg A, Zelano J, Cullheim S (2010) Netrin G-2 ligand mRNA is downregulated in spinal motoneurons after sciatic nerve lesion. NeuroReport 21:782–785PubMed Berg A, Zelano J, Cullheim S (2010) Netrin G-2 ligand mRNA is downregulated in spinal motoneurons after sciatic nerve lesion. NeuroReport 21:782–785PubMed
21.
Zurück zum Zitat Tadagavadi RK, Wang W, Ramesh G (2010) Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol 185:3750–3758PubMed Tadagavadi RK, Wang W, Ramesh G (2010) Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol 185:3750–3758PubMed
22.
Zurück zum Zitat Mirakaj V, Jennewein C, Konig K, Granja T, Rosenberger P (2012) The guidance receptor neogenin promotes pulmonary inflammation during lung injury. FASEB J 26:1549–1558PubMed Mirakaj V, Jennewein C, Konig K, Granja T, Rosenberger P (2012) The guidance receptor neogenin promotes pulmonary inflammation during lung injury. FASEB J 26:1549–1558PubMed
23.
Zurück zum Zitat Konig K, Gatidou D, Granja T, Meier J, Rosenberger P, Mirakaj V (2012) The axonal guidance receptor neogenin promotes acute inflammation. PLoS O ne 7:e32145 Konig K, Gatidou D, Granja T, Meier J, Rosenberger P, Mirakaj V (2012) The axonal guidance receptor neogenin promotes acute inflammation. PLoS O ne 7:e32145
24.
Zurück zum Zitat Kieseier BC, Mathey EK, Sommer C, Hartung HP (2018) Immune-mediated neuropathies. Nat Rev Dis Primers 4:31PubMed Kieseier BC, Mathey EK, Sommer C, Hartung HP (2018) Immune-mediated neuropathies. Nat Rev Dis Primers 4:31PubMed
25.
Zurück zum Zitat Huebner EA, Strittmatter SM (2009) Axon regeneration in the peripheral and central nervous systems. Results Probl Cell Differ 48:339–351PubMedPubMedCentral Huebner EA, Strittmatter SM (2009) Axon regeneration in the peripheral and central nervous systems. Results Probl Cell Differ 48:339–351PubMedPubMedCentral
26.
Zurück zum Zitat Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F (2004) Development and validation of the Neuropathic Pain Symptom Inventory. Pain 108:248–257PubMed Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F (2004) Development and validation of the Neuropathic Pain Symptom Inventory. Pain 108:248–257PubMed
27.
Zurück zum Zitat Von Korff M, Ormel J, Keefe FJ, Dworkin SF (1992) Grading the severity of chronic pain. Pain 50:133–149 Von Korff M, Ormel J, Keefe FJ, Dworkin SF (1992) Grading the severity of chronic pain. Pain 50:133–149
28.
Zurück zum Zitat Hautzinger BM (1993) Allgemeine Depressionsskala. Manual Weinheim Beltz Gesellschaft, Weinheim DOI Hautzinger BM (1993) Allgemeine Depressionsskala. Manual Weinheim Beltz Gesellschaft, Weinheim DOI
29.
Zurück zum Zitat Merkies IS, Schmitz PI, van der Meche FG, Samijn JP, van Doorn PA, Inflammatory Neuropathy C, Treatment G (2003) Connecting impairment, disability, and handicap in immune mediated polyneuropathies. J Neurol Neurosurg Psychiatry 74:99–104PubMedPubMedCentral Merkies IS, Schmitz PI, van der Meche FG, Samijn JP, van Doorn PA, Inflammatory Neuropathy C, Treatment G (2003) Connecting impairment, disability, and handicap in immune mediated polyneuropathies. J Neurol Neurosurg Psychiatry 74:99–104PubMedPubMedCentral
30.
Zurück zum Zitat Vrancken AF, Notermans NC, Jansen GH, Wokke JH, Said G (2004) Progressive idiopathic axonal neuropathy—a comparative clinical and histopathological study with vasculitic neuropathy. J Neurol 251:269–278PubMed Vrancken AF, Notermans NC, Jansen GH, Wokke JH, Said G (2004) Progressive idiopathic axonal neuropathy—a comparative clinical and histopathological study with vasculitic neuropathy. J Neurol 251:269–278PubMed
31.
Zurück zum Zitat Hughes RA (2001) Chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol 50:281–282PubMed Hughes RA (2001) Chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol 50:281–282PubMed
32.
Zurück zum Zitat Eftimov F, van Schaik I (2013) Chronic inflammatory demyelinating polyradiculoneuropathy: update on clinical features, phenotypes and treatment options. Curr Opin Neurol 26:496–502PubMed Eftimov F, van Schaik I (2013) Chronic inflammatory demyelinating polyradiculoneuropathy: update on clinical features, phenotypes and treatment options. Curr Opin Neurol 26:496–502PubMed
33.
Zurück zum Zitat Ayrignac X, Viala K, Koutlidis RM, Taieb G, Stojkovic T, Musset L, Leger JM, Fournier E, Maisonobe T, Bouche P (2013) Sensory chronic inflammatory demyelinating polyneuropathy: an under-recognized entity? Muscle Nerve 48:727–732PubMed Ayrignac X, Viala K, Koutlidis RM, Taieb G, Stojkovic T, Musset L, Leger JM, Fournier E, Maisonobe T, Bouche P (2013) Sensory chronic inflammatory demyelinating polyneuropathy: an under-recognized entity? Muscle Nerve 48:727–732PubMed
34.
Zurück zum Zitat Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P, G. Toronto Diabetic Neuropathy Expert (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33:2285–2293PubMedPubMedCentral Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P, G. Toronto Diabetic Neuropathy Expert (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33:2285–2293PubMedPubMedCentral
35.
Zurück zum Zitat NOESC, Hadden R, Hahn AF, Illa I, Joint Task Force of the EFNS, and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 15:185–195 NOESC, Hadden R, Hahn AF, Illa I, Joint Task Force of the EFNS, and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 15:185–195
36.
Zurück zum Zitat Collins MP, Periquet MI, Mendell JR, Sahenk Z, Nagaraja HN, Kissel JT (2003) Nonsystemic vasculitic neuropathy: insights from a clinical cohort. Neurology 61:623–630PubMed Collins MP, Periquet MI, Mendell JR, Sahenk Z, Nagaraja HN, Kissel JT (2003) Nonsystemic vasculitic neuropathy: insights from a clinical cohort. Neurology 61:623–630PubMed
37.
Zurück zum Zitat Üçeyler N, Geng A, Reiners K, Toyka KV, Sommer C (2015) Non-systemic vasculitic neuropathy: single-center follow-up of 60 patients. J Neurol 262:2092–2100PubMed Üçeyler N, Geng A, Reiners K, Toyka KV, Sommer C (2015) Non-systemic vasculitic neuropathy: single-center follow-up of 60 patients. J Neurol 262:2092–2100PubMed
38.
Zurück zum Zitat Langjahr M, Schubert AL, Sommer C, Uceyler N (2018) Increased pro-inflammatory cytokine gene expression in peripheral blood mononuclear cells of patients with polyneuropathies. J Neurol 265:618–627PubMed Langjahr M, Schubert AL, Sommer C, Uceyler N (2018) Increased pro-inflammatory cytokine gene expression in peripheral blood mononuclear cells of patients with polyneuropathies. J Neurol 265:618–627PubMed
39.
Zurück zum Zitat Üçeyler N, Kafke W, Riediger N, He L, Necula G, Toyka KV, Sommer C (2010) Elevated proinflammatory cytokine expression in affected skin in small fiber neuropathy. Neurology 74:1806–1813PubMed Üçeyler N, Kafke W, Riediger N, He L, Necula G, Toyka KV, Sommer C (2010) Elevated proinflammatory cytokine expression in affected skin in small fiber neuropathy. Neurology 74:1806–1813PubMed
40.
Zurück zum Zitat Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, Rosenberg N, Sommer C, S. European Federation of Neurological (2005) EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol 12:747–758PubMed Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, Rosenberg N, Sommer C, S. European Federation of Neurological (2005) EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol 12:747–758PubMed
41.
Zurück zum Zitat Dyck PJ, Engelstadt J (2005) Pathological alterations of nerves. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy. Elsevier Saunders, Philadelphia, pp 733–829 Dyck PJ, Engelstadt J (2005) Pathological alterations of nerves. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy. Elsevier Saunders, Philadelphia, pp 733–829
42.
Zurück zum Zitat Winer J, Jung CK, Shackel I, Williams PM (1999) Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 270:41–49PubMed Winer J, Jung CK, Shackel I, Williams PM (1999) Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 270:41–49PubMed
43.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(− Delta Delta C(T)) method. Methods 25:402–408CrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(− Delta Delta C(T)) method. Methods 25:402–408CrossRef
44.
Zurück zum Zitat Üçeyler N, Riediger N, Kafke W, Sommer C (2015) Differential gene expression of cytokines and neurotrophic factors in nerve and skin of patients with peripheral neuropathies. J Neurol 262:203–212PubMed Üçeyler N, Riediger N, Kafke W, Sommer C (2015) Differential gene expression of cytokines and neurotrophic factors in nerve and skin of patients with peripheral neuropathies. J Neurol 262:203–212PubMed
45.
Zurück zum Zitat Huber AB, Kolodkin AL, Ginty DD, Cloutier JF (2003) Signaling at the growth cone: ligand–receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26:509–563 Huber AB, Kolodkin AL, Ginty DD, Cloutier JF (2003) Signaling at the growth cone: ligand–receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26:509–563
46.
Zurück zum Zitat Mothe AJ, Tassew NG, Shabanzadeh AP, Penheiro R, Vigouroux RJ, Huang L, Grinnell C, Cui YF, Fung E, Monnier PP, Mueller BK, Tator CH (2017) RGMa inhibition with human monoclonal antibodies promotes regeneration, plasticity and repair, and attenuates neuropathic pain after spinal cord injury. Sci Rep 7:10529PubMedPubMedCentral Mothe AJ, Tassew NG, Shabanzadeh AP, Penheiro R, Vigouroux RJ, Huang L, Grinnell C, Cui YF, Fung E, Monnier PP, Mueller BK, Tator CH (2017) RGMa inhibition with human monoclonal antibodies promotes regeneration, plasticity and repair, and attenuates neuropathic pain after spinal cord injury. Sci Rep 7:10529PubMedPubMedCentral
47.
Zurück zum Zitat Wu CH, Yuan XC, Gao F, Li HP, Cao J, Liu YS, Yu W, Tian B, Meng XF, Shi J, Pan HL, Li M (2016) Netrin-1 contributes to myelinated afferent fiber sprouting and neuropathic pain. Mol Neurobiol 53:5640–5651PubMed Wu CH, Yuan XC, Gao F, Li HP, Cao J, Liu YS, Yu W, Tian B, Meng XF, Shi J, Pan HL, Li M (2016) Netrin-1 contributes to myelinated afferent fiber sprouting and neuropathic pain. Mol Neurobiol 53:5640–5651PubMed
49.
Zurück zum Zitat Marcol W, Kotulska K, Larysz-Brysz M, Kowalik JL (2007) BDNF contributes to animal model neuropathic pain after peripheral nerve transection. Neurosurg Rev 30:235–243 (discussion 243) PubMed Marcol W, Kotulska K, Larysz-Brysz M, Kowalik JL (2007) BDNF contributes to animal model neuropathic pain after peripheral nerve transection. Neurosurg Rev 30:235–243 (discussion 243) PubMed
50.
Zurück zum Zitat Koppes AN, Nordberg AL, Paolillo GM, Goodsell NM, Darwish HA, Zhang L, Thompson DM (2014) Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth. Tissue Eng Part A 20:494–506PubMed Koppes AN, Nordberg AL, Paolillo GM, Goodsell NM, Darwish HA, Zhang L, Thompson DM (2014) Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth. Tissue Eng Part A 20:494–506PubMed
51.
Zurück zum Zitat Wang Y, Li D, Wang G, Chen L, Chen J, Liu Z, Zhang Z, Shen H, Jin Y, Shen Z (2017) The effect of co-transplantation of nerve fibroblasts and Schwann cells on peripheral nerve repair. Int J Biol Sci 13:1507–1519PubMedPubMedCentral Wang Y, Li D, Wang G, Chen L, Chen J, Liu Z, Zhang Z, Shen H, Jin Y, Shen Z (2017) The effect of co-transplantation of nerve fibroblasts and Schwann cells on peripheral nerve repair. Int J Biol Sci 13:1507–1519PubMedPubMedCentral
52.
Zurück zum Zitat Dreesmann L, Mittnacht U, Lietz M, Schlosshauer B (2009) Nerve fibroblast impact on Schwann cell behavior. Eur J Cell Biol 88:285–300PubMed Dreesmann L, Mittnacht U, Lietz M, Schlosshauer B (2009) Nerve fibroblast impact on Schwann cell behavior. Eur J Cell Biol 88:285–300PubMed
Metadaten
Titel
Reduced gene expression of netrin family members in skin and sural nerve specimens of patients with painful peripheral neuropathies
verfasst von
Anna-Lena Schubert
Melissa Held
Claudia Sommer
Nurcan Üçeyler
Publikationsdatum
07.08.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 11/2019
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-019-09496-6

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23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

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