Journal article
Effects of the α2-ADRENORECEPTOR antagonist dexefaroxan on neurogenesis in the olfactory bulb of the adult rat in vivo: Selective protection against neuronal death
Neuroscience, Vol.117(2), pp.281-291
2003
DOI: 10.1016/S0306-4522(02)00757-1
Abstract
A dysfunction of noradrenergic mechanisms originating in the locus coeruleus has been hypothesised to be the critical factor underlying the evolution of central neurodegenerative diseases [Colpaert FC (1994) Noradrenergic mechanism Parkinson’s disease: a theory. In: Noradrenergic mechanisms in Parkinson’s disease (Briley M, Marien M, eds) pp 225–254. Boca Raton, FL, USA: CRC Press Inc.]. α2-Adrenoceptor antagonists, presumably in part by facilitating central noradrenergic transmission, afford neuroprotection in vivo in models of cerebral ischaemia, excitotoxicity and devascularization-induced neurodegeneration. The present study utilised the rat olfactory bulb as a model system for examining the effects of the selective α2-adrenoceptor antagonist dexefaroxan upon determinants of neurogenesis (proliferation, survival and death) in the adult brain in vivo. Cell proliferation (5-bromo-2′-deoxyuridine labelling) and cell death associated with DNA fragmentation (terminal dideoxynucleotidyl transferase-catalysed 2′-deoxyuridine-5′-triphosphate nick end-labelling assay) were quantified following a 7-day treatment with either vehicle or dexefaroxan (0.63 mg/kg i.p., three times daily), followed by a 3-day washout period. The number of terminal dideoxynucleotidyl transferase-catalysed 2′-deoxyuridine-5′-triphosphate nick end-labelling-positive nuclei in the olfactory bulb was lower in dexefaroxan-treated rats, this difference being greatest and significant in the subependymal layer (−52%). In contrast, 5-bromo-2′-deoxyuridine-immunoreactive nuclei were more numerous (+68%) in the bulbs of dexefaroxan-treated rats whilst no differences were detected in the proliferating region of the subventricular zone. Terminal dideoxynucleotidyl transferase-catalysed 2′-deoxyuridine-5′-triphosphate nick end-labelling combination with glial fibrillary acidic protein or neuronal-specific antigen immunohistochemistry revealed that terminal dideoxynucleotidyl transferase-catalysed 2′-deoxyuridine-5′-triphosphate nick end-labelling-positive nuclei were associated primarily with a neuronal cell phenotype. These findings suggest that dexefaroxan increases neuron survival in the olfactory bulb of the adult rat in vivo, putatively as a result of reducing the apoptotic fate of telencephalic stem cell progenies.
Details
- Title: Subtitle
- Effects of the α2-ADRENORECEPTOR antagonist dexefaroxan on neurogenesis in the olfactory bulb of the adult rat in vivo: Selective protection against neuronal death
- Creators
- S BAKER - Laboratoire Neurosciences et Systèmes Sensoriels, CNRS-UMR 5020, Université Claude Bernard-Lyon 1, Boulevard 11 novembre 1918, 69622 Villeurbanne, FranceE MOYSE - Laboratoire Neurosciences et Systèmes Sensoriels, CNRS-UMR 5020, Université Claude Bernard-Lyon 1, Boulevard 11 novembre 1918, 69622 Villeurbanne, FranceF JOURDAN - Laboratoire Neurosciences et Systèmes Sensoriels, CNRS-UMR 5020, Université Claude Bernard-Lyon 1, Boulevard 11 novembre 1918, 69622 Villeurbanne, FranceF COLPAERT - Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres, FranceJ. C MARTEL - Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres, FranceM MARIEN - Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres, France
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.117(2), pp.281-291
- Publisher
- Elsevier; Oxford
- DOI
- 10.1016/S0306-4522(02)00757-1
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Language
- English
- Date published
- 2003
- Academic Unit
- Ophthalmology and Visual Sciences; Biochemistry and Molecular Biology; Iowa Neuroscience Institute
- Record Identifier
- 9984071635302771
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