Axonal injury-dependent induction of the peripheral benzodiazepine receptor in small-diameter adult rat primary sensory neurons.
The peripheral benzodiazepine receptor (PBR), a benzodiazepine but not gamma-aminobutyric acid-binding mitochondrial membrane protein, has roles in steroid production, energy metabolism, cell survival and growth. PBR expression in the nervous system has been reported in non-neuronal glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand, [(3)H]PK11195, in dorsal root ganglion (DRG) neurons following injury to the sciatic nerve. In naïve animals, PBR mRNA, protein expression and ligand binding are undetectable in the DRG. Three days after sciatic nerve transection, however, PBR mRNA begins to be expressed in injured neurons, and 4 weeks after the injury, expression and ligand binding are present in 35% of L4 DRG neurons. PBR ligand binding also appears after injury in the superficial dorsal horn of the spinal cord. The PBR expression in the DRG is restricted to small and medium-sized neurons and returns to naïve levels if the injured peripheral axons are allowed to regrow and reinnervate targets. No non-neuronal PBR expression is detected, unlike its putative endogenous ligand the diazepam binding inhibitor (DBI), which is expressed only in non-neuronal cells, including the satellite cells that surround DRG neurons. DBI expression does not change with sciatic nerve transection. PBR acting on small-calibre neurons could play a role in the adaptive survival and growth responses of these cells to injury of their axons.
Karchewski
Laurie A
LA
Neural Plasticity Research Group, Department of Anaesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, MGH-East, 149 13th Street, Rm 4309, Charlestown, MA 02129, USA. lkarch@igbmc.u-strasbg.fr
Bloechlinger
Stefan
S
Woolf
Clifford J
CJ
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001369:Axons / Q000378:metabolism*; D019771:Axotomy / Q000379:methods; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D048429:Cell Size / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007210:Indoleacetic Acids / Q000378:metabolism; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D009437:Neuralgia / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D007210:Indoleacetic Acids; D007546:Isoquinolines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014316:Tritium; C069997:Tspo protein, rat; C030098:5-methoxy-methylindoleacetic acid; C037850:PK 11195