Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity
Abstract
The peripheral-type benzodiazepine receptor (PBR) is a critical component of the mitochondrial permeability transition pore, which is involved in the regulation of cell survival. Different forms of brain injury result in induction of the expression of the PBR in the areas of neurodegeneration, mainly in reactive glial cells. The consequences of induction of PBR expression after brain injury are unknown. To test whether PBR may be involved in the regulation of neuronal survival after injury, we have assessed the effect of two PBR ligands, Ro5-4864 and PK11195, on neuronal loss induced by kainic acid in the hippocampus. Systemic administration of kainic acid to male rats resulted in the induction of a reactive phenotype in astrocytes and microglia and in a significant loss of hilar neurons in the dentate gyrus. Administration of Ro5-4864, before the injection of kainic acid, decreased reactive gliosis in the hilus and prevented hilar neuronal loss. In contrast, PK11195 was unable to reduce reactive gliosis and did not protect hilar neurons from kainic acid. These findings suggest that the PBR is involved in control of neuronal survival and gliosis after brain injury and identify this molecule as a potential target for neuroprotective interventions.
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TSPO ligands have been shown to prevent neuronal loss in several animal models.
“TSPO ligands have been shown to prevent neuronal loss in several animal models [13;67–69].”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [68]
The apparent effects of TSPO ligands to reduce pathology in animal disease models could be mediated through effects on astrocytes.
“The apparent effects of TSPO ligands to reduce pathology in animal disease models could be mediated through effects on astrocytes (Ryu et al., 2005; Veiga et al., 2005).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Veiga et al., 2005
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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
The mitochondrial permeability transition from<i>in vitro</i>artifact to disease target
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A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis
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“The apparent effects of TSPO ligands to reduce pathology in animal disease models could be mediated through effects on astrocytes (Ryu et al. , 2005; Veiga et al. , 2005).”
Steroidogenic acute regulatory protein in the brain
Lavaque, E., Sierra, A., Azcoitia, I., & Garcia-Segura, L. M. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.05.060 · Cited by 81 · see citing works
Self-citationNeuroprotective effect of Ro5-4864 following brain injury
Soustiel, J. F., Zaaroor, M., Vlodavsky, E., Veenman, L., Weizman, A., & Gavish, M. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.08.008 · Cited by 44 · see citing works
- Authors
- Veiga, S., Azcoitia, I., & Garcia-Segura, L. M.
- Affiliations
- Instituto Cajal (ES)
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2005
- Volume
- 80
- Issue
- 1
- Pages
- 129-137
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2037862528
- Cited by
- 101
- References
- 2
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 10 · 2015: 7 · 2014: 4 · 2013: 10 · 2012: 2
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Ro5-4864, PK11195, translocator protein (TSPO), reactive gliosis, dentate gyrus, astrocytes, microglia, neuroprotection, mitochondrial permeability transition pore, neuronal survival, neurodegeneration
- MeSH terms
- Animals, Benzodiazepinones, Gliosis, Hippocampus, Immunohistochemistry, Isoquinolines, Kainic Acid, Male, Neurons, Vimentin, Rats, Wistar, Receptors, GABA, Excitatory Amino Acid Agonists, Neuroprotective Agents, Rats
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