Role of the peripheral benzodiazepine receptor in sensory neuron regeneration
Abstract
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.
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TSPO is expressed in almost all CNS cells, including astrocytes, neurons and endothelial cells.
“Although increased TSPO expression has historically been mostly associated with microglial activation, TSPO is now known to be expressed in almost all CNS cells including astrocytes, neurons and endothelial cells [21–27], all of which may also be involved in, or be affected by neuroinflammation [28].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [24]
TSPO is present in immature neurons.
“Studies have demonstrated the presence of TSPO in immature neurons, as well as in differentiating/regenerating neurons [23, 24, 52].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [24]
TSPO is present in differentiating/regenerating neurons.
“Studies have demonstrated the presence of TSPO in immature neurons, as well as in differentiating/regenerating neurons [23, 24, 52].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [24]
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References 77 · Cited by 42
- Authors
- Mills, C. D., Bitler, J. L., & Woolf, C. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Mills, Charles D.
- ORCID
- Woolf, Clifford J.
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 30
- Issue
- 2
- Pages
- 228-237
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W1998695313
- Cited by
- 42
- References
- 77
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 038253, NS45459, R01NS038253, F32NS045459)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- translocator protein (TSPO), sensory neuron regeneration, dorsal root ganglia, axon growth, peripheral nerve injury, sciatic nerve crush injury, Ro5-4864, PK11195, peripherin, GAP-43
- MeSH terms
- Animals, Axons, Benzodiazepinones, Cell Survival, Convulsants, Ganglia, Spinal, Isoquinolines, Ligands, Male, Nerve Regeneration, Neurons, Afferent, Peripheral Nerves, Receptors, GABA-A, Neurites, Rats, Sprague-Dawley, In Situ Hybridization, Rats
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