Regulation of the expression of peripheral benzodiazepine receptors and their endogenous ligands during rat sciatic nerve degeneration and regeneration: a role for PBR in neurosteroidogenesis
Abstract
Peripheral benzodiazepine receptors (PBR) and their endogenous ligands, the diazepam-binding inhibitor derived-peptides, are present in Schwann cells in the peripheral nervous system. The aim of this study was to determine the influence of reversible (freeze-injury) and permanent (transection and ligature) nerve lesion on PBR density and on the levels of their endogenous ligands, by autoradiography (using [3H]PK11195) and radioimmunoassay (using antisera directed against the octadecaneuropeptide (ODN), a diazepam-binding inhibitor fragment). The potential role of PBR on peripheral nerve steroidogenesis, was studied by investigating the effect of specific PBR agonists and antagonists on pregnenolone levels in the sciatic nerve. Sixteen to 30 days after nerve lesion, PBR density and ODN-LI level were highly increased. Their expression returned to normal level when regeneration was completed 60 days after freeze-injury, but remained elevated when regeneration did not occur in transected distal stumps. Reverse-phase HPLC analysis of ODN-LI showed that in control nerve extracts, the major immunoreactive peak co-elutes with triakontatetraneuropeptide (TTN). After freeze-injury, intermediate molecular forms eluting between ODN and TTN were predominant and remained elevated at day 60. The greater accumulation of intermediate forms when regeneration is allowed to occur may indicate a particular role of these forms in axonal elongation and myelination. Ro5-4864, a high affinity PBR ago…
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Cholesterol is the necessary precursor for the synthesis of neurosteroids.
“cholesterol which is the necessary precursor for the synthesis of neurosteroids [53–56]”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [55]
TSPO is involved in the mitochondrial intermembrane transport of cholesterol.
“TSPO is involved in the mitochondrial intermembrane transport of cholesterol”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [55]
Cites
Progesterone synthesis and myelin formation by Schwann cells
Koenig, H. L., Schumacher, M., Ferzaz, B., Thi, A. N. D., Ressouches, A., Guennoun, R., Jung-Testas, I., Robel, P., Akwa, Y., & Baulieu, E.-E. (1995) · Science · doi:10.1126/science.7770777 · Cited by 480 · see citing works
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Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T. C., Fan, J., Akula, N., Groyer, G., Adams, D., & Schumacher, M. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3295 · Cited by 930 · see citing works
Self-citationRone, M. B., Fan, J., & Papadopoulos, V. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.03.001 · Cited by 399 · see citing works
Lacapère, J.-J., & Papadopoulos, V. (2003) · Steroids · doi:10.1016/s0039-128x(03)00101-6 · Cited by 342 · see citing works
Ferzaz, B., Brault, E., Bourliaud, G., Robert, J.-P., Poughon, G., Claustre, Y., Marguet, F., Liere, P., Schumacher, M., Nowicki, J.-P., et al. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.301.3.1067 · Cited by 126 · see citing works
Self-citationVicente-Rodríguez, M., Mancuso, R., Peris-Yague, A., Simmons, C., NIMA Consortium, Wlazly, D., Dickinson, A., Foster, A., Knight, C., Leckey, C., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02769-y · Cited by 17 · see citing works
- Authors
- Lacor, P., Gandolfo, P., Tonon, M.-C., Brault, E., Dalibert, I., Schumacher, M., Benavides, J., & Ferzaz, B.
- Affiliations
- Inserm (FR)
- Corresponding author
- Ferzaz, Badia
- ORCID
- Gandolfo, Pierrick
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 815
- Issue
- 1
- Pages
- 70-80
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2058069935
- Cited by
- 114
- References
- 1
- Citations by year
- 2024: 4 · 2023: 1 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 4 · 2014: 1 · 2013: 1 · 2012: 4
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- translocator protein (TSPO), octadecaneuropeptide, nerve regeneration, nerve degeneration, frost damage, nerve transection, ligature, Schwann cells, neurosteroidogenesis, pregnenolone, PK11195, Ro5-4864, axon elongation, myelination, sciatic nerve
- MeSH terms
- Animals, Antineoplastic Agents, Benzodiazepinones, Chromatography, High Pressure Liquid, Convulsants, Freezing, Gene Expression Regulation, Isoquinolines, Ligands, Myelin Sheath, Nerve Regeneration, Neuropeptides, Peptide Fragments, Pregnenolone, Radioimmunoassay, Receptors, GABA-A, Sciatic Nerve, Tritium, Wallerian Degeneration, Rats, Sprague-Dawley, Diazepam Binding Inhibitor, Rats
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