Role of the peripheral benzodiazepine receptor in sensory neuron regeneration.
Peripheral benzodiazepine receptor (PBR) expression increases in small dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury. To determine the functional significance of this induction, we evaluated the effects of PBR ligands on rodent sensory axon outgrowth. In vitro, Ro5-4864, a PBR agonist, enhanced outgrowth only of small peripherin-positive DRG neurons. When DRG cells were preconditioned into an active growth state by a prior peripheral nerve injury Ro5-4864 augmented and PK 11195, a PBR antagonist, blocked the injury-induced increased outgrowth. In vivo, Ro5-4864 increased the initiation of regeneration after a sciatic nerve crush injury and the number of GAP-43-positive axons in the distal nerve while PK 11195 inhibited the enhanced growth produced by a preconditioning lesion. These results show that PBR has a role in the early regenerative response of small caliber sensory axons, the preconditioning effect, and that PBR agonists enhance sensory axon regeneration.
Mills
Charles D
CD
Neural Plasticity Research Group, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA. cmills@hms.harvard.edu
Bitler
Jaquelyn L
JL
Woolf
Clifford J
CJ
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001570:Benzodiazepinones / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D017403:In Situ Hybridization; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; C037850:PK 11195