PMID- 19565659
OWN - NLM
STAT- MEDLINE
DCOM- 20100219
LR  - 20181201
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 58
IP  - 2
DP  - 2010 Jan 15
TI  - Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial 
      cells and selectively modifies neurosteroidogenesis in sensory neurons.
PG  - 169-80
LID - 10.1002/glia.20910 [doi]
AB  - Neurosteroids are synthesized either by glial cells, by neurons, or within the 
      context of neuron-glia cross-talk. Various studies suggested neurosteroid 
      involvement in the control of neurodegeneration but there is no evidence showing 
      that the natural protection of nerve cells against apoptosis directly depends on 
      their own capacity to produce neuroprotective neurosteroids. Here, we 
      investigated the interactions between neurosteroidogenesis and apoptosis 
      occurring in sensory structures of rats subjected to neuropathic pain generated 
      by sciatic nerve chronic constriction injury (CCI). Using the terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), we observed 
      no apoptotic cells in the spinal cord up to 30 days after CCI although pain 
      symptoms such as mechano-allodynia, thermal and mechanical hyperalgesia were 
      evidenced with the Hargreaves's behavioral and von Frey filament tests. In 
      contrast, double-labeling experiments combining TUNEL and immunostaining with 
      antibodies against glutamine synthetase or neuronal nuclei protein revealed 
      apoptosis occurrence in satellite glial cells (SGC) (not in neurons) of CCI rat 
      ipsilateral dorsal root ganglia (DRG) at day 30 after injury. Pulse-chase 
      experiments coupled with high performance liquid chromatography and flow 
      scintillation detection showed that, among numerous biosynthetic pathways 
      converting [(3)H]pregnenolone into various [(3)H]neurosteroids, only 
      [(3)H]estradiol formation was selectively modified and upregulated in DRG of CCI 
      rats. Consistently, immunohistochemical investigations localized aromatase 
      (estradiol-synthesizing enzyme) in DRG neurons but not in SGC. Pharmacological 
      inhibition of aromatase caused apoptosis of CCI rat DRG neurons. Altogether, our 
      results suggest that endogenously produced neurosteroids such as estradiol may be 
      pivotal for the protection of DRG sensory neurons against sciatic nerve 
      CCI-induced apoptosis.
FAU - Schaeffer, Veronique
AU  - Schaeffer V
AD  - Equipe Steroides, Neuromodulateurs et Neuropathologies, Universite de Strasbourg, 
      Unite de Physiopathologie et Medecine Translationnelle, Batiment 3 de la Faculte 
      de Medecine, 11 rue Humann, Strasbourg, France.
FAU - Meyer, Laurence
AU  - Meyer L
FAU - Patte-Mensah, Christine
AU  - Patte-Mensah C
FAU - Eckert, Anne
AU  - Eckert A
FAU - Mensah-Nyagan, Ayikoe G
AU  - Mensah-Nyagan AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Nitriles)
RN  - 0 (Triazoles)
RN  - 4TI98Z838E (Estradiol)
RN  - 73R90F7MQ8 (Pregnenolone)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 1.14.14.1 (Aromatase)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Aromatase/metabolism
MH  - Aromatase Inhibitors/pharmacology
MH  - Cell Survival/drug effects
MH  - Estradiol/metabolism
MH  - Ganglia, Spinal/drug effects/enzymology/*physiopathology
MH  - Letrozole
MH  - Male
MH  - Neuroglia/drug effects/enzymology/*physiology
MH  - Neurotransmitter Agents/*metabolism
MH  - Nitriles/pharmacology
MH  - Pain/enzymology/etiology/*physiopathology
MH  - Pain Measurement
MH  - Pregnenolone/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sciatic Nerve/*injuries/physiopathology
MH  - Sensory Receptor Cells/drug effects/enzymology/*physiology
MH  - Time Factors
MH  - Triazoles/pharmacology
EDAT- 2009/07/01 09:00
MHDA- 2010/02/20 06:00
CRDT- 2009/07/01 09:00
PHST- 2009/07/01 09:00 [entrez]
PHST- 2009/07/01 09:00 [pubmed]
PHST- 2010/02/20 06:00 [medline]
AID - 10.1002/glia.20910 [doi]
PST - ppublish
SO  - Glia. 2010 Jan 15;58(2):169-80. doi: 10.1002/glia.20910.