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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...

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Autores principales: Lee, Michelle, Cheng, Melody M, Lin, Chi-Ying, Louis, Elan D, Faust, Phyllis L, Kuo, Sheng-Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
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.
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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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