The University of Southampton
University of Southampton Institutional Repository

Sigma receptor agonist 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury

Sigma receptor agonist 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury
Sigma receptor agonist 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury
Spinal root avulsion leads to a progressive loss of axotomized motoneurons (MNs). Nowadays, there is no effective treatment to prolong MN survival that could permit recovery as a result of delayed surgical repair. Administration of Sigma-1 receptor (Sig-1R) ligands has been reported to promote beneficial effects after several types of neural injury. In order to shed light of whether Sig-1R ligands could promote MN survival after root avulsion, L4-L5 spinal roots were unilaterally avulsed in adult rats and the Sig-1R agonist Pre084 was administered at different doses. The ventral spinal cords of the animals were studied from 3 to 21 days post-operation (DPO) by using histological, immunohistochemical, and Western blot techniques. Daily treatment with 0.25?mg/kg Pre084 significantly promoted MN survival (68% vs 43% in untreated rats) at 21 DPO, an effect that was antagonized by coadministration of BD1063, an antagonist of Sig-1R. There was a reduction in astroglial- associated immunoreactivity in rats treated with Pre084. Moreover, Pre084 produced an increase in the Sig-1R co-chaperone BiP within MNs, and an increase of GDNF expression by astrocytes in the ventral horn early after injury. Although the mechanisms promoting MN survival by Pre084 remain unclear, we hypothesize that it is mediated at least in part through the increase in these cytoprotective factors. Therefore, early application of Sig-1R agonist appears to be a promising therapy to improve MN survival after root avulsion
0897-7151
831-840
Penas, Clara
650c6d8e-5990-4765-9a66-2b43fbfe46a1
Pascual-Font, Arán
6be8299a-9e9f-4913-aa12-c6db1900be1a
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Forés, Joaquim
1d575c83-7f51-44e0-be2b-7d33af405cdf
Casas, Caty
1fe75d94-4fac-4719-ba06-9ccf810385ec
Navarro, Xavier
8854ebaa-d283-4d46-829e-c7c8f186585e
Penas, Clara
650c6d8e-5990-4765-9a66-2b43fbfe46a1
Pascual-Font, Arán
6be8299a-9e9f-4913-aa12-c6db1900be1a
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Forés, Joaquim
1d575c83-7f51-44e0-be2b-7d33af405cdf
Casas, Caty
1fe75d94-4fac-4719-ba06-9ccf810385ec
Navarro, Xavier
8854ebaa-d283-4d46-829e-c7c8f186585e

Penas, Clara, Pascual-Font, Arán, Mancuso, Renzo, Forés, Joaquim, Casas, Caty and Navarro, Xavier (2011) Sigma receptor agonist 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury. Journal of Neurotrauma, 28 (5), 831-840. (doi:10.1089/neu.2010.1674). (PMID:21332255)

Record type: Article

Abstract

Spinal root avulsion leads to a progressive loss of axotomized motoneurons (MNs). Nowadays, there is no effective treatment to prolong MN survival that could permit recovery as a result of delayed surgical repair. Administration of Sigma-1 receptor (Sig-1R) ligands has been reported to promote beneficial effects after several types of neural injury. In order to shed light of whether Sig-1R ligands could promote MN survival after root avulsion, L4-L5 spinal roots were unilaterally avulsed in adult rats and the Sig-1R agonist Pre084 was administered at different doses. The ventral spinal cords of the animals were studied from 3 to 21 days post-operation (DPO) by using histological, immunohistochemical, and Western blot techniques. Daily treatment with 0.25?mg/kg Pre084 significantly promoted MN survival (68% vs 43% in untreated rats) at 21 DPO, an effect that was antagonized by coadministration of BD1063, an antagonist of Sig-1R. There was a reduction in astroglial- associated immunoreactivity in rats treated with Pre084. Moreover, Pre084 produced an increase in the Sig-1R co-chaperone BiP within MNs, and an increase of GDNF expression by astrocytes in the ventral horn early after injury. Although the mechanisms promoting MN survival by Pre084 remain unclear, we hypothesize that it is mediated at least in part through the increase in these cytoprotective factors. Therefore, early application of Sig-1R agonist appears to be a promising therapy to improve MN survival after root avulsion

Full text not available from this repository.

More information

e-pub ahead of print date: 18 February 2011
Published date: May 2011
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 376118
URI: http://eprints.soton.ac.uk/id/eprint/376118
ISSN: 0897-7151
PURE UUID: 3f0d3871-d94b-40bd-adc9-d14a1590b4d6

Catalogue record

Date deposited: 24 Apr 2015 11:00
Last modified: 15 Jul 2019 21:23

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×