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Decreased EAAT2 protein expression in the essential tremor cerebellar cortex

Michelle Lee; Melody Cheng; Chi-Ying Lin; Elan D. Louis; Phyllis L. Faust; Sheng-Han Kuo

Title:
Decreased EAAT2 protein expression in the essential tremor cerebellar cortex
Author(s):
Lee, Michelle
Cheng, Melody
Lin, Chi-Ying
Louis, Elan D.
Faust, Phyllis L.
Kuo, Sheng-Han
Date:
Type:
Articles
Department(s):
Neurology
Epidemiology
Pathology and Cell Biology
Volume:
2
Persistent URL:
Book/Journal Title:
Acta Neuropathologica Communications
Publisher:
BioMed Central
Abstract:
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.
Subject(s):
Neurosciences
Publisher DOI:
https://doi.org/10.1186/s40478-014-0157-z
Item views
236
Metadata:
text | xml
Suggested Citation:
Michelle Lee, Melody Cheng, Chi-Ying Lin, Elan D. Louis, Phyllis L. Faust, Sheng-Han Kuo, , Decreased EAAT2 protein expression in the essential tremor cerebellar cortex, Columbia University Academic Commons, .

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