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TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia
For decades, the glial function has been highlighted not only as the ‘structural glue’, but also as an ‘active participant’ in neural circuits. Here, we suggest that tumor necrosis factor α (TNF-α), a key inflammatory cytokine, alters the neural activity of the cerebellar Purkinje cells (PCs) by fac...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072779/ https://www.ncbi.nlm.nih.gov/pubmed/30072733 http://dx.doi.org/10.1038/s41598-018-29786-9 |
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author | Shim, Hyun Geun Jang, Sung-Soo Kim, Seung Ha Hwang, Eun Mi Min, Joo Ok Kim, Hye Yun Kim, Yoo Sung Ryu, Changhyeon Chung, Geehoon Kim, YoungSoo Yoon, Bo-Eun Kim, Sang Jeong |
author_facet | Shim, Hyun Geun Jang, Sung-Soo Kim, Seung Ha Hwang, Eun Mi Min, Joo Ok Kim, Hye Yun Kim, Yoo Sung Ryu, Changhyeon Chung, Geehoon Kim, YoungSoo Yoon, Bo-Eun Kim, Sang Jeong |
author_sort | Shim, Hyun Geun |
collection | PubMed |
description | For decades, the glial function has been highlighted not only as the ‘structural glue’, but also as an ‘active participant’ in neural circuits. Here, we suggest that tumor necrosis factor α (TNF-α), a key inflammatory cytokine, alters the neural activity of the cerebellar Purkinje cells (PCs) by facilitating gliotransmission in the juvenile male rat cerebellum. A bath application of TNF-α (100 ng/ml) in acute cerebellar slices elevates spiking activity of PCs with no alterations in the regularity of PC firings. Interestingly, the effect of TNF-α on the intrinsic excitability of PCs was abolished under a condition in which the type1 TNF receptor (TNFR1) in Bergmann glia (BG) was genetically suppressed by viral delivery of an adeno-associated virus (AAV) containing TNFR1-shRNA. In addition, we measured the concentration of glutamate derived from dissociated cerebellar cortical astrocyte cultures treated with TNF-α and observed a progressive increase of glutamate in a time-dependent manner. We hypothesised that TNF-α-induced elevation of glutamate from BGs enveloping the synaptic cleft may directly activate metabotropic glutamate receptor1 (mGluR1). Pharmacological inhibition of mGluR1, indeed, prevented the TNF-α-mediated elevation of the intrinsic excitability in PCs. Taken together, our study reveals that TNF-α triggers glutamate release in BG, thereby increasing the intrinsic excitability of cerebellar PCs in a mGluR1-dependent manner. |
format | Online Article Text |
id | pubmed-6072779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60727792018-08-07 TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia Shim, Hyun Geun Jang, Sung-Soo Kim, Seung Ha Hwang, Eun Mi Min, Joo Ok Kim, Hye Yun Kim, Yoo Sung Ryu, Changhyeon Chung, Geehoon Kim, YoungSoo Yoon, Bo-Eun Kim, Sang Jeong Sci Rep Article For decades, the glial function has been highlighted not only as the ‘structural glue’, but also as an ‘active participant’ in neural circuits. Here, we suggest that tumor necrosis factor α (TNF-α), a key inflammatory cytokine, alters the neural activity of the cerebellar Purkinje cells (PCs) by facilitating gliotransmission in the juvenile male rat cerebellum. A bath application of TNF-α (100 ng/ml) in acute cerebellar slices elevates spiking activity of PCs with no alterations in the regularity of PC firings. Interestingly, the effect of TNF-α on the intrinsic excitability of PCs was abolished under a condition in which the type1 TNF receptor (TNFR1) in Bergmann glia (BG) was genetically suppressed by viral delivery of an adeno-associated virus (AAV) containing TNFR1-shRNA. In addition, we measured the concentration of glutamate derived from dissociated cerebellar cortical astrocyte cultures treated with TNF-α and observed a progressive increase of glutamate in a time-dependent manner. We hypothesised that TNF-α-induced elevation of glutamate from BGs enveloping the synaptic cleft may directly activate metabotropic glutamate receptor1 (mGluR1). Pharmacological inhibition of mGluR1, indeed, prevented the TNF-α-mediated elevation of the intrinsic excitability in PCs. Taken together, our study reveals that TNF-α triggers glutamate release in BG, thereby increasing the intrinsic excitability of cerebellar PCs in a mGluR1-dependent manner. Nature Publishing Group UK 2018-08-02 /pmc/articles/PMC6072779/ /pubmed/30072733 http://dx.doi.org/10.1038/s41598-018-29786-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shim, Hyun Geun Jang, Sung-Soo Kim, Seung Ha Hwang, Eun Mi Min, Joo Ok Kim, Hye Yun Kim, Yoo Sung Ryu, Changhyeon Chung, Geehoon Kim, YoungSoo Yoon, Bo-Eun Kim, Sang Jeong TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia |
title | TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia |
title_full | TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia |
title_fullStr | TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia |
title_full_unstemmed | TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia |
title_short | TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia |
title_sort | tnf-α increases the intrinsic excitability of cerebellar purkinje cells through elevating glutamate release in bergmann glia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072779/ https://www.ncbi.nlm.nih.gov/pubmed/30072733 http://dx.doi.org/10.1038/s41598-018-29786-9 |
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