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Involvement of ceramide in ethanol-induced apoptotic neurodegeneration in the neonatal mouse brain
- Source :
- Journal of Neurochemistry. 115:168-177
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Acute administration of ethanol to 7-day-old mice is known to cause robust apoptotic neurodegeneration in the brain. Our previous studies have shown that such ethanol-induced neurodegeneration is accompanied by increases in lipids, including ceramide, triglyceride (TG), cholesterol ester (ChE), and N-acylphosphatidylethanolamine (NAPE) in the brain. In this study, the effects of ethanol on lipid profiles as well as caspase 3 activation were examined in the cortex, hippocampus, cerebellum, and inferior colliculus of the postnatal day 7 mouse brain. We found that the cortex, hippocampus, and inferior colliculus, which showed substantial caspase 3 activation by ethanol, manifested significant elevations in ceramide, TG, and NAPE. In contrast, the cerebellum, with the least caspase 3 activation, failed to show significant changes in ceramide and TG, and exhibits much smaller increases in NAPE than other brain regions. Ethanol-induced increases in ChE were observed in all brain regions tested. Inhibitors of serine palmitoyltransferase effectively blocked ethanol-induced caspase 3 activation as well as elevations in ceramide, ChE, and NAPE. Immunohistochemical studies indicated that the expression of serine palmitoyltransferase was mainly localized in neurons and was enhanced in activated caspase 3-positive neurons generated by ethanol. These results indicate that de novo ceramide synthesis has a vital role in ethanol-induced apoptotic neurodegeneration in the developing brain.
- Subjects :
- medicine.medical_specialty
Cerebellum
Ceramide
Nape
biology
Neurodegeneration
Central nervous system
Hippocampus
Caspase 3
medicine.disease
Biochemistry
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Endocrinology
medicine.anatomical_structure
chemistry
Internal medicine
medicine
biology.protein
Caspase
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi...........b703ed4e3b922558ce7c35db19594508