Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord

Cinzia Brandoli, Bitao Shi, Beth Pflug, Peter Andrews, Jean R. Wrathall, Italo Mocchetti

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Apoptosis is an important cause of secondary cell death in spinal cord injury (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75 (p75NTR), that in the absence of the high affinity component, TrkA, can promote cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR expression in SCI may increase tissue sparing and therefore improve recovery of function. As a tool to test our hypothesis we used the synthetic glucocorticoid dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic spinal cord contusion injury was produced in female rats. Laminectomized and SCI rats received various doses of DEX immediately after injury and the treatment was continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI rats, without affecting the expression of TrkA. High doses of DEX also reduced cellular apoptosis both in white and gray matters. This effect correlated with the ability of DEX to accelerate behavioral recovery of function measured by a combined behavioral score. These data suggest that reduction of p75NTR in SCI may be a therapeutic strategy to limit cell and tissue damage and therefore to improve recovery of function in SCI patients.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalMolecular Brain Research
Volume87
Issue number1
DOIs
StatePublished - Feb 19 2001

Fingerprint

Nerve Growth Factor Receptor
Contusions
Spinal Cord Injuries
Dexamethasone
Spinal Cord
Apoptosis
Recovery of Function
Cell Death
Glucocorticoids
Thorax
Down-Regulation
Messenger RNA

Keywords

  • Glucocorticoid
  • Spinal cord injury
  • TrkA
  • p75NTR

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord. / Brandoli, Cinzia; Shi, Bitao; Pflug, Beth; Andrews, Peter; Wrathall, Jean R.; Mocchetti, Italo.

In: Molecular Brain Research, Vol. 87, No. 1, 19.02.2001, p. 61-70.

Research output: Contribution to journalArticle

Brandoli, Cinzia ; Shi, Bitao ; Pflug, Beth ; Andrews, Peter ; Wrathall, Jean R. ; Mocchetti, Italo. / Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord. In: Molecular Brain Research. 2001 ; Vol. 87, No. 1. pp. 61-70.
@article{4226383193924897932045da43d15b29,
title = "Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord",
abstract = "Apoptosis is an important cause of secondary cell death in spinal cord injury (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75 (p75NTR), that in the absence of the high affinity component, TrkA, can promote cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR expression in SCI may increase tissue sparing and therefore improve recovery of function. As a tool to test our hypothesis we used the synthetic glucocorticoid dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic spinal cord contusion injury was produced in female rats. Laminectomized and SCI rats received various doses of DEX immediately after injury and the treatment was continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI rats, without affecting the expression of TrkA. High doses of DEX also reduced cellular apoptosis both in white and gray matters. This effect correlated with the ability of DEX to accelerate behavioral recovery of function measured by a combined behavioral score. These data suggest that reduction of p75NTR in SCI may be a therapeutic strategy to limit cell and tissue damage and therefore to improve recovery of function in SCI patients.",
keywords = "Glucocorticoid, Spinal cord injury, TrkA, p75NTR",
author = "Cinzia Brandoli and Bitao Shi and Beth Pflug and Peter Andrews and Wrathall, {Jean R.} and Italo Mocchetti",
year = "2001",
month = "2",
day = "19",
doi = "10.1016/S0169-328X(00)00284-9",
language = "English (US)",
volume = "87",
pages = "61--70",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord

AU - Brandoli, Cinzia

AU - Shi, Bitao

AU - Pflug, Beth

AU - Andrews, Peter

AU - Wrathall, Jean R.

AU - Mocchetti, Italo

PY - 2001/2/19

Y1 - 2001/2/19

N2 - Apoptosis is an important cause of secondary cell death in spinal cord injury (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75 (p75NTR), that in the absence of the high affinity component, TrkA, can promote cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR expression in SCI may increase tissue sparing and therefore improve recovery of function. As a tool to test our hypothesis we used the synthetic glucocorticoid dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic spinal cord contusion injury was produced in female rats. Laminectomized and SCI rats received various doses of DEX immediately after injury and the treatment was continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI rats, without affecting the expression of TrkA. High doses of DEX also reduced cellular apoptosis both in white and gray matters. This effect correlated with the ability of DEX to accelerate behavioral recovery of function measured by a combined behavioral score. These data suggest that reduction of p75NTR in SCI may be a therapeutic strategy to limit cell and tissue damage and therefore to improve recovery of function in SCI patients.

AB - Apoptosis is an important cause of secondary cell death in spinal cord injury (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75 (p75NTR), that in the absence of the high affinity component, TrkA, can promote cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR expression in SCI may increase tissue sparing and therefore improve recovery of function. As a tool to test our hypothesis we used the synthetic glucocorticoid dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic spinal cord contusion injury was produced in female rats. Laminectomized and SCI rats received various doses of DEX immediately after injury and the treatment was continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI rats, without affecting the expression of TrkA. High doses of DEX also reduced cellular apoptosis both in white and gray matters. This effect correlated with the ability of DEX to accelerate behavioral recovery of function measured by a combined behavioral score. These data suggest that reduction of p75NTR in SCI may be a therapeutic strategy to limit cell and tissue damage and therefore to improve recovery of function in SCI patients.

KW - Glucocorticoid

KW - Spinal cord injury

KW - TrkA

KW - p75NTR

UR - http://www.scopus.com/inward/record.url?scp=0035910921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035910921&partnerID=8YFLogxK

U2 - 10.1016/S0169-328X(00)00284-9

DO - 10.1016/S0169-328X(00)00284-9

M3 - Article

C2 - 11223160

AN - SCOPUS:0035910921

VL - 87

SP - 61

EP - 70

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -