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Páll Karlsson

Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth

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Molecular and cellular correlates of human nerve regeneration : ADCYAP1/PACAP enhance nerve outgrowth. / Baskozos, Georgios; Sandy-Hindmarch, Oliver; Clark, Alex J; Windsor, Katherine; Karlsson, Pall; Weir, Greg A; McDermott, Lucy A; Burchall, Joanna; Wiberg, Akira; Furniss, Dominic; Bennett, David L H; Schmid, Annina B.

I: Brain : a journal of neurology, Bind 143, Nr. 7, 07.2020, s. 2009-2026.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Baskozos, G, Sandy-Hindmarch, O, Clark, AJ, Windsor, K, Karlsson, P, Weir, GA, McDermott, LA, Burchall, J, Wiberg, A, Furniss, D, Bennett, DLH & Schmid, AB 2020, 'Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth', Brain : a journal of neurology, bind 143, nr. 7, s. 2009-2026. https://doi.org/10.1093/brain/awaa163

APA

Baskozos, G., Sandy-Hindmarch, O., Clark, A. J., Windsor, K., Karlsson, P., Weir, G. A., McDermott, L. A., Burchall, J., Wiberg, A., Furniss, D., Bennett, D. L. H., & Schmid, A. B. (2020). Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth. Brain : a journal of neurology, 143(7), 2009-2026. https://doi.org/10.1093/brain/awaa163

CBE

Baskozos G, Sandy-Hindmarch O, Clark AJ, Windsor K, Karlsson P, Weir GA, McDermott LA, Burchall J, Wiberg A, Furniss D, Bennett DLH, Schmid AB. 2020. Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth. Brain : a journal of neurology. 143(7):2009-2026. https://doi.org/10.1093/brain/awaa163

MLA

Vancouver

Baskozos G, Sandy-Hindmarch O, Clark AJ, Windsor K, Karlsson P, Weir GA o.a. Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth. Brain : a journal of neurology. 2020 jul;143(7):2009-2026. https://doi.org/10.1093/brain/awaa163

Author

Baskozos, Georgios ; Sandy-Hindmarch, Oliver ; Clark, Alex J ; Windsor, Katherine ; Karlsson, Pall ; Weir, Greg A ; McDermott, Lucy A ; Burchall, Joanna ; Wiberg, Akira ; Furniss, Dominic ; Bennett, David L H ; Schmid, Annina B. / Molecular and cellular correlates of human nerve regeneration : ADCYAP1/PACAP enhance nerve outgrowth. I: Brain : a journal of neurology. 2020 ; Bind 143, Nr. 7. s. 2009-2026.

Bibtex

@article{aa020014935d4c4398c0d19a4f18c03e,
title = "Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth",
abstract = "We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relationship with clinical recovery. In 60 patients undergoing carpal tunnel surgery [36 female, mean age 62.5 (standard deviation 12.2) years], we used quantitative sensory testing and nerve conduction studies to evaluate the function of large and small fibres before and 6 months after surgery. Clinical recovery was assessed with the global rating of change scale and Boston Carpal Tunnel Questionnaire. Twenty healthy participants provided normative data [14 female, mean age 58.0 (standard deviation 12.9) years]. At 6 months post-surgery, we noted significant recovery of median nerve neurophysiological parameters (P < 0.0001) and improvements in quantitative sensory testing measures of both small and large nerve fibre function (P < 0.002). Serial biopsies revealed a partial recovery of intraepidermal nerve fibre density [fibres/mm epidermis pre: 4.20 (2.83), post: 5.35 (3.34), P = 0.001], whose extent correlated with symptom improvement (r = 0.389, P = 0.001). In myelinated afferents, nodal length increased postoperatively [pre: 2.03 (0.82), post: 3.03 (1.23), P < 0.0001] suggesting that this is an adaptive phenomenon. Transcriptional profiling of the skin revealed 31 differentially expressed genes following decompression, with ADCYAP1 (encoding pituitary adenylate cyclase activating peptide, PACAP) being the most strongly upregulated (log2 fold-change 1.87, P = 0.0001) and its expression was associated with recovery of intraepidermal nerve fibres. We found that human induced pluripotent stem cell-derived sensory neurons expressed the receptor for PACAP and that this peptide could significantly enhance axon outgrowth in a dose-dependent manner in vitro [neurite length PACAP 1065.0 µm (285.5), vehicle 570.9 μm (181.8), P = 0.003]. In conclusion, carpal tunnel release is associated with significant cutaneous reinnervation, which correlates with the degree of functional improvement and is associated with a transcriptional programme relating to morphogenesis and inflammatory processes. The most highly dysregulated gene ADCYAP1 (encoding PACAP) was associated with reinnervation and, given that this peptide signals through G-protein coupled receptors, this signalling pathway provides an interesting therapeutic target for human sensory nerve regeneration.",
author = "Georgios Baskozos and Oliver Sandy-Hindmarch and Clark, {Alex J} and Katherine Windsor and Pall Karlsson and Weir, {Greg A} and McDermott, {Lucy A} and Joanna Burchall and Akira Wiberg and Dominic Furniss and Bennett, {David L H} and Schmid, {Annina B}",
note = "{\textcopyright} The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.",
year = "2020",
month = jul,
doi = "10.1093/brain/awaa163",
language = "English",
volume = "143",
pages = "2009--2026",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "7",

}

RIS

TY - JOUR

T1 - Molecular and cellular correlates of human nerve regeneration

T2 - ADCYAP1/PACAP enhance nerve outgrowth

AU - Baskozos, Georgios

AU - Sandy-Hindmarch, Oliver

AU - Clark, Alex J

AU - Windsor, Katherine

AU - Karlsson, Pall

AU - Weir, Greg A

AU - McDermott, Lucy A

AU - Burchall, Joanna

AU - Wiberg, Akira

AU - Furniss, Dominic

AU - Bennett, David L H

AU - Schmid, Annina B

N1 - © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.

PY - 2020/7

Y1 - 2020/7

N2 - We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relationship with clinical recovery. In 60 patients undergoing carpal tunnel surgery [36 female, mean age 62.5 (standard deviation 12.2) years], we used quantitative sensory testing and nerve conduction studies to evaluate the function of large and small fibres before and 6 months after surgery. Clinical recovery was assessed with the global rating of change scale and Boston Carpal Tunnel Questionnaire. Twenty healthy participants provided normative data [14 female, mean age 58.0 (standard deviation 12.9) years]. At 6 months post-surgery, we noted significant recovery of median nerve neurophysiological parameters (P < 0.0001) and improvements in quantitative sensory testing measures of both small and large nerve fibre function (P < 0.002). Serial biopsies revealed a partial recovery of intraepidermal nerve fibre density [fibres/mm epidermis pre: 4.20 (2.83), post: 5.35 (3.34), P = 0.001], whose extent correlated with symptom improvement (r = 0.389, P = 0.001). In myelinated afferents, nodal length increased postoperatively [pre: 2.03 (0.82), post: 3.03 (1.23), P < 0.0001] suggesting that this is an adaptive phenomenon. Transcriptional profiling of the skin revealed 31 differentially expressed genes following decompression, with ADCYAP1 (encoding pituitary adenylate cyclase activating peptide, PACAP) being the most strongly upregulated (log2 fold-change 1.87, P = 0.0001) and its expression was associated with recovery of intraepidermal nerve fibres. We found that human induced pluripotent stem cell-derived sensory neurons expressed the receptor for PACAP and that this peptide could significantly enhance axon outgrowth in a dose-dependent manner in vitro [neurite length PACAP 1065.0 µm (285.5), vehicle 570.9 μm (181.8), P = 0.003]. In conclusion, carpal tunnel release is associated with significant cutaneous reinnervation, which correlates with the degree of functional improvement and is associated with a transcriptional programme relating to morphogenesis and inflammatory processes. The most highly dysregulated gene ADCYAP1 (encoding PACAP) was associated with reinnervation and, given that this peptide signals through G-protein coupled receptors, this signalling pathway provides an interesting therapeutic target for human sensory nerve regeneration.

AB - We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relationship with clinical recovery. In 60 patients undergoing carpal tunnel surgery [36 female, mean age 62.5 (standard deviation 12.2) years], we used quantitative sensory testing and nerve conduction studies to evaluate the function of large and small fibres before and 6 months after surgery. Clinical recovery was assessed with the global rating of change scale and Boston Carpal Tunnel Questionnaire. Twenty healthy participants provided normative data [14 female, mean age 58.0 (standard deviation 12.9) years]. At 6 months post-surgery, we noted significant recovery of median nerve neurophysiological parameters (P < 0.0001) and improvements in quantitative sensory testing measures of both small and large nerve fibre function (P < 0.002). Serial biopsies revealed a partial recovery of intraepidermal nerve fibre density [fibres/mm epidermis pre: 4.20 (2.83), post: 5.35 (3.34), P = 0.001], whose extent correlated with symptom improvement (r = 0.389, P = 0.001). In myelinated afferents, nodal length increased postoperatively [pre: 2.03 (0.82), post: 3.03 (1.23), P < 0.0001] suggesting that this is an adaptive phenomenon. Transcriptional profiling of the skin revealed 31 differentially expressed genes following decompression, with ADCYAP1 (encoding pituitary adenylate cyclase activating peptide, PACAP) being the most strongly upregulated (log2 fold-change 1.87, P = 0.0001) and its expression was associated with recovery of intraepidermal nerve fibres. We found that human induced pluripotent stem cell-derived sensory neurons expressed the receptor for PACAP and that this peptide could significantly enhance axon outgrowth in a dose-dependent manner in vitro [neurite length PACAP 1065.0 µm (285.5), vehicle 570.9 μm (181.8), P = 0.003]. In conclusion, carpal tunnel release is associated with significant cutaneous reinnervation, which correlates with the degree of functional improvement and is associated with a transcriptional programme relating to morphogenesis and inflammatory processes. The most highly dysregulated gene ADCYAP1 (encoding PACAP) was associated with reinnervation and, given that this peptide signals through G-protein coupled receptors, this signalling pathway provides an interesting therapeutic target for human sensory nerve regeneration.

U2 - 10.1093/brain/awaa163

DO - 10.1093/brain/awaa163

M3 - Journal article

C2 - 32651949

VL - 143

SP - 2009

EP - 2026

JO - Brain

JF - Brain

SN - 0006-8950

IS - 7

ER -