Ethanol causes and lithium prevents neuroapoptosis and suppression of pERK in the infant mouse brain.
Transient exposure of immature animals during the brain growth spurt period to ethanol triggers neuroapoptosis in the developing brain. Here we report that lithium, when administered in a single, well-tolerated dose to infant mice, suppresses spontaneous neuroapoptosis that occurs naturally in the developing brain, and prevents ethanol from triggering neuroapoptosis. To explore lithium's mechanism of action, we focused on kinase signaling systems (ERK, Akt, JNK) that are believed to play a regulatory role in cell survival, and found that very rapidly after ethanol administration there is a suppression of ERK phosphorylation, and that lithium stimulates ERK phosphorylation and prevents ethanol from suppressing this phosphorylation process. Ethanol also suppressed pAKT, but lithium did not counteract this effect. We also found that ethanol activates the JNK system, but this cannot explain the neurotoxic action of ethanol, because JNK activation did not occur in the same neuronal populations that are killed by ethanol.
Young
Chainllie
C
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA.
Straiko
Megan M W
MM
Johnson
Stephen A
SA
Creeley
Catherine
C
Olney
John W
JW
D020268:Alcohol-Induced Disorders, Nervous System / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D018692:Antimanic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D018020:Lithium Compounds / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects
D018692:Antimanic Agents; D002492:Central Nervous System Depressants; D018020:Lithium Compounds; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases