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Decreased EAAT2 protein expression in the essential tremor cerebellar cortex
Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essent...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239402/ https://www.ncbi.nlm.nih.gov/pubmed/25391854 http://dx.doi.org/10.1186/s40478-014-0157-z |
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author | Lee, Michelle Cheng, Melody M Lin, Chi-Ying Louis, Elan D Faust, Phyllis L Kuo, Sheng-Han |
author_facet | Lee, Michelle Cheng, Melody M Lin, Chi-Ying Louis, Elan D Faust, Phyllis L Kuo, Sheng-Han |
author_sort | Lee, Michelle |
collection | PubMed |
description | Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-014-0157-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4239402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42394022014-11-21 Decreased EAAT2 protein expression in the essential tremor cerebellar cortex Lee, Michelle Cheng, Melody M Lin, Chi-Ying Louis, Elan D Faust, Phyllis L Kuo, Sheng-Han Acta Neuropathol Commun Research Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-014-0157-z) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-13 /pmc/articles/PMC4239402/ /pubmed/25391854 http://dx.doi.org/10.1186/s40478-014-0157-z Text en © Lee et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Lee, Michelle Cheng, Melody M Lin, Chi-Ying Louis, Elan D Faust, Phyllis L Kuo, Sheng-Han Decreased EAAT2 protein expression in the essential tremor cerebellar cortex |
title | Decreased EAAT2 protein expression in the essential tremor cerebellar cortex |
title_full | Decreased EAAT2 protein expression in the essential tremor cerebellar cortex |
title_fullStr | Decreased EAAT2 protein expression in the essential tremor cerebellar cortex |
title_full_unstemmed | Decreased EAAT2 protein expression in the essential tremor cerebellar cortex |
title_short | Decreased EAAT2 protein expression in the essential tremor cerebellar cortex |
title_sort | decreased eaat2 protein expression in the essential tremor cerebellar cortex |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239402/ https://www.ncbi.nlm.nih.gov/pubmed/25391854 http://dx.doi.org/10.1186/s40478-014-0157-z |
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