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

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-3{beta} (GSK-3{beta}), 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-3{beta}, 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-3{beta}, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways.

Authors:
 [1];  [2];  [3];  [2]; ;  [1];  [1];  [2];  [1];  [4]
  1. Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States)
  2. (United States)
  3. Division of Analytical Psychopharmacology, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States)
  4. (United States), E-mail: marsaito@nki.rfmh.org
Publication Date:
OSTI Identifier:
21043657
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 367; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2008.01.004; PII: S0006-291X(08)00023-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMP; APOPTOSIS; BRAIN; CHOLESTEROL; ESTERS; ETHANOL; GLYCOGEN; LIPIDS; LITHIUM; MICE; MODULATION; PHOSPHORYLATION; PHOSPHOTRANSFERASES

Citation Formats

Chakraborty, Goutam, Department of Chemistry and Biochemistry, Montclair State University, Upper Montclair, NJ 07043, Saito, Mitsuo, Department of Psychiatry, New York University Medical Center, New York, NY 10016, Mao, Rui-Fen, Wang, Ray, Vadasz, Csaba, Department of Psychiatry, New York University Medical Center, New York, NY 10016, Saito, Mariko, and Department of Psychiatry, New York University Medical Center, New York, NY 10016. Lithium blocks ethanol-induced modulation of protein kinases in the developing brain. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.01.004.
Chakraborty, Goutam, Department of Chemistry and Biochemistry, Montclair State University, Upper Montclair, NJ 07043, Saito, Mitsuo, Department of Psychiatry, New York University Medical Center, New York, NY 10016, Mao, Rui-Fen, Wang, Ray, Vadasz, Csaba, Department of Psychiatry, New York University Medical Center, New York, NY 10016, Saito, Mariko, & Department of Psychiatry, New York University Medical Center, New York, NY 10016. Lithium blocks ethanol-induced modulation of protein kinases in the developing brain. United States. doi:10.1016/j.bbrc.2008.01.004.
Chakraborty, Goutam, Department of Chemistry and Biochemistry, Montclair State University, Upper Montclair, NJ 07043, Saito, Mitsuo, Department of Psychiatry, New York University Medical Center, New York, NY 10016, Mao, Rui-Fen, Wang, Ray, Vadasz, Csaba, Department of Psychiatry, New York University Medical Center, New York, NY 10016, Saito, Mariko, and Department of Psychiatry, New York University Medical Center, New York, NY 10016. 2008. "Lithium blocks ethanol-induced modulation of protein kinases in the developing brain". United States. doi:10.1016/j.bbrc.2008.01.004.
@article{osti_21043657,
title = {Lithium blocks ethanol-induced modulation of protein kinases in the developing brain},
author = {Chakraborty, Goutam and Department of Chemistry and Biochemistry, Montclair State University, Upper Montclair, NJ 07043 and Saito, Mitsuo and Department of Psychiatry, New York University Medical Center, New York, NY 10016 and Mao, Rui-Fen and Wang, Ray and Vadasz, Csaba and Department of Psychiatry, New York University Medical Center, New York, NY 10016 and Saito, Mariko and Department of Psychiatry, New York University Medical Center, New York, NY 10016},
abstractNote = {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-3{beta} (GSK-3{beta}), 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-3{beta}, 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-3{beta}, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways.},
doi = {10.1016/j.bbrc.2008.01.004},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 367,
place = {United States},
year = 2008,
month = 3
}
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