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Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices

The cholinergic system plays a major role in learning and cognition and cholinergic neurons appear to be particularly vulnerable to ethanol (EtOH) exposure. There are conflicting results if EtOH directly damages cholinergic neurons. Thus, the aims of the present study were (1) to investigate the eff...

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Autores principales: Ehrlich, Daniela, Pirchl, Michael, Humpel, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier/North-Holland Biomedical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370645/
https://www.ncbi.nlm.nih.gov/pubmed/22560095
http://dx.doi.org/10.1016/j.brainres.2012.04.020
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author Ehrlich, Daniela
Pirchl, Michael
Humpel, Christian
author_facet Ehrlich, Daniela
Pirchl, Michael
Humpel, Christian
author_sort Ehrlich, Daniela
collection PubMed
description The cholinergic system plays a major role in learning and cognition and cholinergic neurons appear to be particularly vulnerable to ethanol (EtOH) exposure. There are conflicting results if EtOH directly damages cholinergic neurons. Thus, the aims of the present study were (1) to investigate the effect of different EtOH concentrations on cholinergic neurons in organotypic brain slices of the nucleus basalis of Meynert (nbM) and (2) to study if the most potent cholinotrophic substance nerve growth factor (NGF) or inhibitors of mitogen activated kinase (MAPK) p38- and nitric-oxide synthase (NOS)-pathways may counteract any EtOH effect. Two-week old organotypic rat brain slices of the nbM were exposed to 1–100 mM EtOH for 7 days with or without drugs and the number of choline-acetyltransferase (ChAT)-positive neurons was counted. Our data show that EtOH significantly reduced the number of ChAT-positive neurons with the most potent effect at a concentration of 50 mM EtOH (54 ± 5 neurons per slice, p < 0.001), compared to control slices (120 ± 13 neurons per slice). Inhibition of MAPK p38 (SB 203580, 10 μM) and NOS (L-thiocitrulline, 10 μM) counteracted the EtOH-induced decline of cholinergic neurons and NGF protected cholinergic neurons against the EtOH-induced effect. Withdrawal of EtOH resulted in a reversal of cholinergic neurons to nearly controls. In conclusion, EtOH caused a transient decline of cholinergic neurons, possibly involving MAPK p38- and NOS-pathways suggesting that EtOH does not induce direct cell death, but causes a transient downregulation of the cholinergic key enzyme, possibly reflecting a form of EtOH-associated plasticity.
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spelling pubmed-33706452012-06-18 Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices Ehrlich, Daniela Pirchl, Michael Humpel, Christian Brain Res Research Report The cholinergic system plays a major role in learning and cognition and cholinergic neurons appear to be particularly vulnerable to ethanol (EtOH) exposure. There are conflicting results if EtOH directly damages cholinergic neurons. Thus, the aims of the present study were (1) to investigate the effect of different EtOH concentrations on cholinergic neurons in organotypic brain slices of the nucleus basalis of Meynert (nbM) and (2) to study if the most potent cholinotrophic substance nerve growth factor (NGF) or inhibitors of mitogen activated kinase (MAPK) p38- and nitric-oxide synthase (NOS)-pathways may counteract any EtOH effect. Two-week old organotypic rat brain slices of the nbM were exposed to 1–100 mM EtOH for 7 days with or without drugs and the number of choline-acetyltransferase (ChAT)-positive neurons was counted. Our data show that EtOH significantly reduced the number of ChAT-positive neurons with the most potent effect at a concentration of 50 mM EtOH (54 ± 5 neurons per slice, p < 0.001), compared to control slices (120 ± 13 neurons per slice). Inhibition of MAPK p38 (SB 203580, 10 μM) and NOS (L-thiocitrulline, 10 μM) counteracted the EtOH-induced decline of cholinergic neurons and NGF protected cholinergic neurons against the EtOH-induced effect. Withdrawal of EtOH resulted in a reversal of cholinergic neurons to nearly controls. In conclusion, EtOH caused a transient decline of cholinergic neurons, possibly involving MAPK p38- and NOS-pathways suggesting that EtOH does not induce direct cell death, but causes a transient downregulation of the cholinergic key enzyme, possibly reflecting a form of EtOH-associated plasticity. Elsevier/North-Holland Biomedical Press 2012-06-12 /pmc/articles/PMC3370645/ /pubmed/22560095 http://dx.doi.org/10.1016/j.brainres.2012.04.020 Text en © 2012 Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Research Report
Ehrlich, Daniela
Pirchl, Michael
Humpel, Christian
Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices
title Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices
title_full Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices
title_fullStr Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices
title_full_unstemmed Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices
title_short Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices
title_sort ethanol transiently suppresses choline-acetyltransferase in basal nucleus of meynert slices
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370645/
https://www.ncbi.nlm.nih.gov/pubmed/22560095
http://dx.doi.org/10.1016/j.brainres.2012.04.020
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