Low-potency glucocorticoid hydrocortisone has similar neurotoxic effects as high-potency glucocorticoid dexamethasone on neurons in the immature chicken cerebellum

Abstract High-potency glucocorticoids (GC) are used in the prophylaxis and treatment of neonatal bronchopulmonal dysplasia, but there is concern about side effects on the developing brain. Recently, the low-potency GC hydrocortisone (HC) has been suggested as an alternative to high-potency GC. We co...

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Veröffentlicht in:Brain research 2008-10, Vol.1236, p.39-48
Hauptverfasser: Aden, Petra, Goverud, Ingeborg, Liestøl, Knut, Løberg, Else Marit, Paulsen, Ragnhild E, Mæhlen, Jan, Lømo, Jon
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container_title Brain research
container_volume 1236
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Goverud, Ingeborg
Liestøl, Knut
Løberg, Else Marit
Paulsen, Ragnhild E
Mæhlen, Jan
Lømo, Jon
description Abstract High-potency glucocorticoids (GC) are used in the prophylaxis and treatment of neonatal bronchopulmonal dysplasia, but there is concern about side effects on the developing brain. Recently, the low-potency GC hydrocortisone (HC) has been suggested as an alternative to high-potency GC. We compared the neurotoxic effects of HC with the high-potency GC dexamethasone (DEX) in chicken cerebellum. A single dose of GC was injected into the egg at embryonic day 16 and the death of granule neurons in histologic sections of the cerebellar cortex was examined 24 h later. DEX and HC showed a similar dose-dependent induction of morphological apoptosis and caspase-3 activation in the internal granular layer. A doubling of the apoptosis rate compared to the basal rate was seen for the highest dose of DEX (5 mg/kg) and medium dose of HC (1 mg/kg). In cultures of embryonic chicken cerebellar granule cells, DEX and HC increased cell death and induced rapid caspase-3 activation in a similar dose-dependent manner. Transfection of granule cells with a luciferase reporter gene revealed that the dose needed for the activation of gene transcription (classical signalling pathway) with DEX was much lower than for HC. In conclusion, HC does not present itself as a safer drug than DEX in this model. In addition, it appears that DEX and HC induce apoptosis in immature granule neurons via a non-genomic (non-classical) mechanism.
doi_str_mv 10.1016/j.brainres.2008.07.095
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Recently, the low-potency GC hydrocortisone (HC) has been suggested as an alternative to high-potency GC. We compared the neurotoxic effects of HC with the high-potency GC dexamethasone (DEX) in chicken cerebellum. A single dose of GC was injected into the egg at embryonic day 16 and the death of granule neurons in histologic sections of the cerebellar cortex was examined 24 h later. DEX and HC showed a similar dose-dependent induction of morphological apoptosis and caspase-3 activation in the internal granular layer. A doubling of the apoptosis rate compared to the basal rate was seen for the highest dose of DEX (5 mg/kg) and medium dose of HC (1 mg/kg). In cultures of embryonic chicken cerebellar granule cells, DEX and HC increased cell death and induced rapid caspase-3 activation in a similar dose-dependent manner. Transfection of granule cells with a luciferase reporter gene revealed that the dose needed for the activation of gene transcription (classical signalling pathway) with DEX was much lower than for HC. In conclusion, HC does not present itself as a safer drug than DEX in this model. In addition, it appears that DEX and HC induce apoptosis in immature granule neurons via a non-genomic (non-classical) mechanism.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2008.07.095</identifier><identifier>PMID: 18706896</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Apoptosis - drug effects ; Biological and medical sciences ; Caspase 3 - metabolism ; Caspase Inhibitors ; Cells, Cultured ; Cerebellar development ; Cerebellum - cytology ; Chick Embryo - drug effects ; Development. Senescence. Regeneration. 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Transfection of granule cells with a luciferase reporter gene revealed that the dose needed for the activation of gene transcription (classical signalling pathway) with DEX was much lower than for HC. In conclusion, HC does not present itself as a safer drug than DEX in this model. In addition, it appears that DEX and HC induce apoptosis in immature granule neurons via a non-genomic (non-classical) mechanism.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase Inhibitors</subject><subject>Cells, Cultured</subject><subject>Cerebellar development</subject><subject>Cerebellum - cytology</subject><subject>Chick Embryo - drug effects</subject><subject>Development. Senescence. Regeneration. 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Senescence. Regeneration. Transplantation</topic><topic>Dexamethasone - toxicity</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. 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Transfection of granule cells with a luciferase reporter gene revealed that the dose needed for the activation of gene transcription (classical signalling pathway) with DEX was much lower than for HC. In conclusion, HC does not present itself as a safer drug than DEX in this model. In addition, it appears that DEX and HC induce apoptosis in immature granule neurons via a non-genomic (non-classical) mechanism.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>18706896</pmid><doi>10.1016/j.brainres.2008.07.095</doi><tpages>10</tpages></addata></record>
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source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Animals
Apoptosis - drug effects
Biological and medical sciences
Caspase 3 - metabolism
Caspase Inhibitors
Cells, Cultured
Cerebellar development
Cerebellum - cytology
Chick Embryo - drug effects
Development. Senescence. Regeneration. Transplantation
Dexamethasone - toxicity
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Glucocorticoids
Glucocorticoids - toxicity
Hydrocortisone - toxicity
Indoles
Neurology
Neurons - drug effects
Neurotoxicity
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - metabolism
Transcription, Genetic - drug effects
Transfection
Vertebrates: nervous system and sense organs
title Low-potency glucocorticoid hydrocortisone has similar neurotoxic effects as high-potency glucocorticoid dexamethasone on neurons in the immature chicken cerebellum
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