Ethanol causes and lithium prevents neuroapoptosis and suppression of pERK in the infant mouse brain
Autor: | John W. Olney, Catherine E. Creeley, Chainllie Young, Megan M.W. Straiko, Stephen A. Johnson |
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Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Lithium (medication) MAP Kinase Signaling System Apoptosis Biology Article lcsh:RC321-571 Phosphorylation Process Mice chemistry.chemical_compound Alcohol-Induced Disorders Nervous System Antimanic Agents Internal medicine medicine Animals Drug Interactions Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase B lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Ethanol JNK Mitogen-Activated Protein Kinases Brain Central Nervous System Depressants Cell biology Enzyme Activation Mice Inbred C57BL Erk phosphorylation Disease Models Animal Endocrinology Brain growth Animals Newborn Neurology Mechanism of action chemistry Nerve Degeneration Lithium Compounds medicine.symptom medicine.drug |
Zdroj: | Neurobiology of Disease, Vol 31, Iss 3, Pp 355-360 (2008) |
Popis: | 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. |
Databáze: | OpenAIRE |
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