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PMID: 18190791 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Lithium blocks ethanol-induced modulation of protein kinases in the developing brain.

Biochemical and biophysical research communications ·Vol. 367 ·No. 3 ·2008-03-14 ·Pages 597-602

Chakraborty G, Saito M, Mao RF, Wang R, Vadasz C, Saito M

Abstract

Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegeneration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3beta (GSK-3beta), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3beta, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3beta, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways.

MeSH Terms
AMP-Activated Protein Kinases Animals Animals, Newborn Brain/drug effects,growth & development Caspase 3/metabolism Cholesterol Esters/metabolism Enzyme Activation/drug effects Ethanol/antagonists & inhibitors,pharmacology Glycogen Synthase Kinase 3/drug effects,metabolism Glycogen Synthase Kinase 3 beta Injections, Intraperitoneal Lithium Chloride/pharmacology Mice Mice, Inbred C57BL Multienzyme Complexes/drug effects,metabolism Phosphatidylethanolamines/metabolism Phosphorylation/drug effects Protein Kinases/drug effects,metabolism Protein Serine-Threonine Kinases/drug effects,metabolism Proto-Oncogene Proteins c-akt/drug effects,metabolism tau Proteins/metabolism
Chemicals
Cholesterol Esters Multienzyme Complexes Phosphatidylethanolamines tau Proteins Ethanol Protein Kinases Glycogen Synthase Kinase 3 beta Gsk3b protein, mouse Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Glycogen Synthase Kinase 3 AMP-Activated Protein Kinases Caspase 3 Lithium Chloride
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chakraborty Goutam
Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
Saito Mitsuo
Mao Rui-Fen
Wang Ray
Vadasz Csaba
Saito Mariko
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Article Info
Journal
Biochemical and biophysical research communications
Abbr.
Biochem Biophys Res Commun
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.01.004
Published
2008-03-14
Epub
2008-00-09
Pages
597-602
Language
English
Region
United States
NLM ID
0372516
PMCID
PMC2279304
Subset
IM
Grants
NIAAA NIH HHS · R01 AA015355 · United States
NIAAA NIH HHS · R01 AA015355-02 · United States
NIAAA NIH HHS · R01 AA015355-03 · United States
External Links
PubMed source DOI: 10.1016/j.bbrc.2008.01.004 PMC Full Text View journal details
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