Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field
In the central nervous system, interleukin (IL)-3 has been shown to exert a trophic action only on septal cholinergic neurons in vitro and in vivo, but a widespread distribution of IL-3 receptor (IL-3R) in the brain does not conform to such a selective central action of the ligand. Moreover, the mec...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1998
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213360/ https://www.ncbi.nlm.nih.gov/pubmed/9705946 |
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author | Wen, Tong-Chun Tanaka, Junya Peng, Hui Desaki, Junzo Matsuda, Seiji Maeda, Nobuji Fujita, Hiroko Sato, Kohji Sakanaka, Masahiro |
author_facet | Wen, Tong-Chun Tanaka, Junya Peng, Hui Desaki, Junzo Matsuda, Seiji Maeda, Nobuji Fujita, Hiroko Sato, Kohji Sakanaka, Masahiro |
author_sort | Wen, Tong-Chun |
collection | PubMed |
description | In the central nervous system, interleukin (IL)-3 has been shown to exert a trophic action only on septal cholinergic neurons in vitro and in vivo, but a widespread distribution of IL-3 receptor (IL-3R) in the brain does not conform to such a selective central action of the ligand. Moreover, the mechanism(s) underlying the neurotrophic action of IL-3 has not been elucidated, although an erythroleukemic cell line is known to enter apoptosis after IL-3 starvation possibly due to a rapid decrease in Bcl-2 expression. This in vivo study focused on whether IL-3 rescued noncholinergic hippocampal neurons from lethal ischemic damage by modulating the expression of Bcl-x(L), a Bcl-2 family protein produced in the mature brain. 7-d IL-3 infusion into the lateral ventricle of gerbils with transient forebrain ischemia prevented significantly hippocampal CA1 neuron death and ischemia-induced learning disability. TUNEL (terminal deoxynucleotidyltransferase–mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling) staining revealed that IL-3 infusion caused a significant reduction in the number of CA1 neurons exhibiting DNA fragmentation 7 d after ischemia. The neuroprotective action of IL-3 appeared to be mediated by a postischemic transient upregulation of the IL-3R α subunit in the hippocampal CA1 field where IL-3Rα was barely detectable under normal conditions. In situ hybridization histochemistry and immunoblot analysis demonstrated that Bcl-x(L) mRNA expression, even though upregulated transiently in CA1 pyramidal neurons after ischemia, did not lead to the production of Bcl-x(L) protein in ischemic gerbils infused with vehicle. However, IL-3 infusion prevented the decrease in Bcl-x(L) protein expression in the CA1 field of ischemic gerbils. Subsequent in vitro experiments showed that IL-3 induced the expression of Bcl-x(L) mRNA and protein in cultured neurons with IL-3Rα and attenuated neuronal damage caused by a free radical–producing agent FeSO(4). These findings suggest that IL-3 prevents delayed neuronal death in the hippocampal CA1 field through a receptor-mediated expression of Bcl-x(L) protein, which is known to facilitate neuron survival. Since IL-3Rα in the hippocampal CA1 region, even though upregulated in response to ischemic insult, is much less intensely expressed than that in the CA3 region tolerant to ischemia, the paucity of IL-3R interacting with the ligand may account for the vulnerability of CA1 neurons to ischemia. |
format | Text |
id | pubmed-2213360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22133602008-04-16 Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field Wen, Tong-Chun Tanaka, Junya Peng, Hui Desaki, Junzo Matsuda, Seiji Maeda, Nobuji Fujita, Hiroko Sato, Kohji Sakanaka, Masahiro J Exp Med Articles In the central nervous system, interleukin (IL)-3 has been shown to exert a trophic action only on septal cholinergic neurons in vitro and in vivo, but a widespread distribution of IL-3 receptor (IL-3R) in the brain does not conform to such a selective central action of the ligand. Moreover, the mechanism(s) underlying the neurotrophic action of IL-3 has not been elucidated, although an erythroleukemic cell line is known to enter apoptosis after IL-3 starvation possibly due to a rapid decrease in Bcl-2 expression. This in vivo study focused on whether IL-3 rescued noncholinergic hippocampal neurons from lethal ischemic damage by modulating the expression of Bcl-x(L), a Bcl-2 family protein produced in the mature brain. 7-d IL-3 infusion into the lateral ventricle of gerbils with transient forebrain ischemia prevented significantly hippocampal CA1 neuron death and ischemia-induced learning disability. TUNEL (terminal deoxynucleotidyltransferase–mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling) staining revealed that IL-3 infusion caused a significant reduction in the number of CA1 neurons exhibiting DNA fragmentation 7 d after ischemia. The neuroprotective action of IL-3 appeared to be mediated by a postischemic transient upregulation of the IL-3R α subunit in the hippocampal CA1 field where IL-3Rα was barely detectable under normal conditions. In situ hybridization histochemistry and immunoblot analysis demonstrated that Bcl-x(L) mRNA expression, even though upregulated transiently in CA1 pyramidal neurons after ischemia, did not lead to the production of Bcl-x(L) protein in ischemic gerbils infused with vehicle. However, IL-3 infusion prevented the decrease in Bcl-x(L) protein expression in the CA1 field of ischemic gerbils. Subsequent in vitro experiments showed that IL-3 induced the expression of Bcl-x(L) mRNA and protein in cultured neurons with IL-3Rα and attenuated neuronal damage caused by a free radical–producing agent FeSO(4). These findings suggest that IL-3 prevents delayed neuronal death in the hippocampal CA1 field through a receptor-mediated expression of Bcl-x(L) protein, which is known to facilitate neuron survival. Since IL-3Rα in the hippocampal CA1 region, even though upregulated in response to ischemic insult, is much less intensely expressed than that in the CA3 region tolerant to ischemia, the paucity of IL-3R interacting with the ligand may account for the vulnerability of CA1 neurons to ischemia. The Rockefeller University Press 1998-08-17 /pmc/articles/PMC2213360/ /pubmed/9705946 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Wen, Tong-Chun Tanaka, Junya Peng, Hui Desaki, Junzo Matsuda, Seiji Maeda, Nobuji Fujita, Hiroko Sato, Kohji Sakanaka, Masahiro Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field |
title | Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field |
title_full | Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field |
title_fullStr | Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field |
title_full_unstemmed | Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field |
title_short | Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field |
title_sort | interleukin 3 prevents delayed neuronal death in the hippocampal ca1 field |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213360/ https://www.ncbi.nlm.nih.gov/pubmed/9705946 |
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