Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons

Sophie Pezet, Achillefs Spyropoulos, Robert J Williams, Stephen B McMahon

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.
Original languageEnglish
Pages (from-to)1785-97
Number of pages13
JournalEuropean Journal of Neuroscience
Volume21
Issue number7
DOIs
Publication statusPublished - 2005

Fingerprint

Spinal Ganglia
Phosphorylation
Neurons
Nociceptors
Sciatic Nerve
Phosphatidylinositol 3-Kinase
Unmyelinated Nerve Fibers
Protein-Serine-Threonine Kinases
Capsaicin
Tetrodotoxin
Electric Stimulation
Signal Transduction
Cell Survival
Staining and Labeling
Injections

Cite this

Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons. / Pezet, Sophie; Spyropoulos, Achillefs; Williams, Robert J; McMahon, Stephen B.

In: European Journal of Neuroscience, Vol. 21, No. 7, 2005, p. 1785-97.

Research output: Contribution to journalArticle

Pezet, Sophie ; Spyropoulos, Achillefs ; Williams, Robert J ; McMahon, Stephen B. / Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons. In: European Journal of Neuroscience. 2005 ; Vol. 21, No. 7. pp. 1785-97.
@article{f28b40ff9dcd493db6b384799d78c18f,
title = "Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons",
abstract = "The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.",
author = "Sophie Pezet and Achillefs Spyropoulos and Williams, {Robert J} and McMahon, {Stephen B}",
year = "2005",
doi = "10.1111/j.1460-9568.2005.04011.x",
language = "English",
volume = "21",
pages = "1785--97",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons

AU - Pezet, Sophie

AU - Spyropoulos, Achillefs

AU - Williams, Robert J

AU - McMahon, Stephen B

PY - 2005

Y1 - 2005

N2 - The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.

AB - The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.

UR - http://dx.doi.org/10.1111/j.1460-9568.2005.04011.x

U2 - 10.1111/j.1460-9568.2005.04011.x

DO - 10.1111/j.1460-9568.2005.04011.x

M3 - Article

VL - 21

SP - 1785

EP - 1797

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 7

ER -