Ethanol increases retinoic acid production in cerebellar astrocytes and in cerebellum
| Autor: | Peter McCaffery, Na Chen, Deborah Smith, Joseph L. Napoli, M. David Ullman, Omanand Koul |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Cerebellum Retinal dehydrogenase Immunoblotting Retinoic acid Tretinoin Endogeny Biology Cytoplasmic Granules Rats Sprague-Dawley chemistry.chemical_compound Developmental Neuroscience In vivo Internal medicine medicine Animals RNA Messenger Cells Cultured Alcohol dehydrogenase Ethanol Reverse Transcriptase Polymerase Chain Reaction Alcohol Dehydrogenase Central Nervous System Depressants Retinal Dehydrogenase Aldehyde Oxidoreductases Stimulation Chemical Rats Endocrinology medicine.anatomical_structure chemistry Biochemistry Astrocytes biology.protein Developmental Biology medicine.drug Morphogen |
| Zdroj: | Developmental Brain Research. 153:233-241 |
| ISSN: | 0165-3806 |
| Popis: | Several characteristics of fetal alcohol syndrome (FAS) are similar to the teratogenic effects of retinoic acid (RA) exposure. It has been suggested that FAS may result from ethanol-induced alteration in endogenous RA synthesis, leading to abnormal embryonic concentrations of this morphogen. We examined whether ethanol may interfere with RA synthesis in the postnatal cerebellum, as a region of the developing CNS particularly vulnerable to both ethanol and RA teratogenesis. It was found that astrocytes are the predominant source of postnatal RA synthesis in the cerebellum. They express both retinaldehyde dehydrogenase 1 and 2. In vitro cytosolic preparations of astrocytes, as well as live cell preparations, have an increased capacity to synthesize RA in the presence of ethanol. A mechanism by which ethanol could stimulate RA synthesis is via the ethanol-activated short-chain retinol dehydrogenases, which we show to be present in the postnatal cerebellum. To determine whether ethanol stimulated RA synthesis in vivo, a sensitive and highly specific HPLC/MSn technique was used to measure cerebellar RA after administration of ethanol to postnatal day 4 rat pups. Cerebellar RA levels climbed significantly after such treatment. These results suggest that the cerebellar pathology exerted by ethanol may occur, at least in part, through increased production of RA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect