Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats

Tzer Bin Lin, Cheng Yuan Lai, Ming Chun Hsieh, Jian Lin Jiang, Jen Kun Cheng, Yat Pang Chau, Ting Ruan, Gin Den Chen, Hsien Yu Peng

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1 (Nrx1b), regulating clustering of N-methyl-d-Aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-Associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-Associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)-Associated allodynia. Methods: In 626 adult male Sprague-Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. Results: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1-PSD-95, pNR2B-PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95-pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1-PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95-pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6). Conclusion: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b-NL1 interactions.

Original languageEnglish
Pages (from-to)909-926
Number of pages18
JournalAnesthesiology
Volume123
Issue number4
Publication statusPublished - Oct 1 2015

Fingerprint

Post-Synaptic Density
Hyperalgesia
Spinal Nerves
Ligation
neuroligin 1
Small Interfering RNA
Learning
Antisense RNA
Neuronal Plasticity
Fluorescent Antibody Technique
Sprague Dawley Rats
Cluster Analysis

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Lin, T. B., Lai, C. Y., Hsieh, M. C., Jiang, J. L., Cheng, J. K., Chau, Y. P., ... Peng, H. Y. (2015). Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats. Anesthesiology, 123(4), 909-926.

Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats. / Lin, Tzer Bin; Lai, Cheng Yuan; Hsieh, Ming Chun; Jiang, Jian Lin; Cheng, Jen Kun; Chau, Yat Pang; Ruan, Ting; Chen, Gin Den; Peng, Hsien Yu.

In: Anesthesiology, Vol. 123, No. 4, 01.10.2015, p. 909-926.

Research output: Contribution to journalArticle

Lin, TB, Lai, CY, Hsieh, MC, Jiang, JL, Cheng, JK, Chau, YP, Ruan, T, Chen, GD & Peng, HY 2015, 'Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats', Anesthesiology, vol. 123, no. 4, pp. 909-926.
Lin, Tzer Bin ; Lai, Cheng Yuan ; Hsieh, Ming Chun ; Jiang, Jian Lin ; Cheng, Jen Kun ; Chau, Yat Pang ; Ruan, Ting ; Chen, Gin Den ; Peng, Hsien Yu. / Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats. In: Anesthesiology. 2015 ; Vol. 123, No. 4. pp. 909-926.
@article{0881e902e1604ed29bca08146b6b32b2,
title = "Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats",
abstract = "Background: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1 (Nrx1b), regulating clustering of N-methyl-d-Aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-Associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-Associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)-Associated allodynia. Methods: In 626 adult male Sprague-Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. Results: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1-PSD-95, pNR2B-PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95-pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1-PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95-pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6). Conclusion: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b-NL1 interactions.",
author = "Lin, {Tzer Bin} and Lai, {Cheng Yuan} and Hsieh, {Ming Chun} and Jiang, {Jian Lin} and Cheng, {Jen Kun} and Chau, {Yat Pang} and Ting Ruan and Chen, {Gin Den} and Peng, {Hsien Yu}",
year = "2015",
month = "10",
day = "1",
language = "English",
volume = "123",
pages = "909--926",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats

AU - Lin, Tzer Bin

AU - Lai, Cheng Yuan

AU - Hsieh, Ming Chun

AU - Jiang, Jian Lin

AU - Cheng, Jen Kun

AU - Chau, Yat Pang

AU - Ruan, Ting

AU - Chen, Gin Den

AU - Peng, Hsien Yu

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Background: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1 (Nrx1b), regulating clustering of N-methyl-d-Aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-Associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-Associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)-Associated allodynia. Methods: In 626 adult male Sprague-Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. Results: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1-PSD-95, pNR2B-PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95-pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1-PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95-pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6). Conclusion: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b-NL1 interactions.

AB - Background: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1 (Nrx1b), regulating clustering of N-methyl-d-Aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-Associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-Associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)-Associated allodynia. Methods: In 626 adult male Sprague-Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. Results: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1-PSD-95, pNR2B-PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95-pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1-PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95-pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6). Conclusion: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b-NL1 interactions.

UR - http://www.scopus.com/inward/record.url?scp=84942040953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942040953&partnerID=8YFLogxK

M3 - Article

C2 - 26263430

AN - SCOPUS:84942040953

VL - 123

SP - 909

EP - 926

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 4

ER -