Ethanol alters lipid profiles and phosphorylation status of AMP-activated protein kinase in the neonatal mouse brain.
Previously, we have shown that ethanol-induced apoptosis in cultured neurons is accompanied by changes in cellular lipid profiles. In the present study, the effects of ethanol on brain lipid metabolism were studied using 7-day-old C57BL/6ByJ mice, which display apoptotic neurodegeneration upon exposure to ethanol. The brain lipids were extracted 4-24 h after the ethanol or saline treatment, and analyzed by TLC. We found that the levels of triglyceride, cholesterol ester, ceramide, and N-acylphosphatidylethanolamine increased significantly in the brains of ethanol-treated mice compared to those of saline-treated mice. Concomitantly, ethanol reduced Thr172 phosphorylation of AMP-activated protein kinase (AMPK) alpha subunits. Ethanol also reduced phosphorylation of acetyl-CoA carboxylase, a substrate of AMPK and a lipogenic enzyme known to be activated by dephosphorylation. In contrast, lipid profiles of 19-day-old mouse brains, which scarcely manifested neurodegeneration upon ethanol exposure, were not significantly affected by ethanol. Also, the basal levels of Thr172-phosphorylated AMPK alpha were lower in these brains than in 7-day-old mouse brains, and no detectable changes in the phosphorylation status were observed by ethanol treatment. Our findings indicate that the ethanol-induced apoptotic neurodegeneration observed in mice during restricted developmental periods is accompanied by alterations in both the lipid content and the activity of AMPK in the brain.
Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA. marsaito@nki.rfmh.org
Mariko
M
Saito
Goutam
G
Chakraborty
Rui-Fen
RF
Mao
Ray
R
Wang
Thomas B
TB
Cooper
Csaba
C
Vadasz
Mitsuo
M
Saito
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002518:Ceramides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008563:Membrane Lipids / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D002492:Central Nervous System Depressants; D002518:Ceramides; D008563:Membrane Lipids; D009097:Multienzyme Complexes; D014280:Triglycerides; D000431:Ethanol; D002784:Cholesterol; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase