SLC1A2 rs3794087 variant and risk for migraine
JOURNAL OF THE NEUROLOGICAL SCIENCES
Authors: Garcia-Martin, Elena; Martinez, Carmen; Serrador, Mercedes; Alonso-Navarro, Hortensia; Navacerrada, Francisco; Agundez, Jose A. G.; Javier Jimenez-Jimenez, Felix
Abstract
Background/objectives: Glutamate has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism rs3794087 in the SLC1A2 gene (EATT2 or GLT-1; chromosome 11p13-p12 involved in glutamate transport) and the risk for migraine and for triggering migraine attacks by alcohol. Methods: We studied the frequency of the rs3794087 genotypes and allelic variants in 197 patients with migraine and 308 healthy controls using a TaqMan-based qPCR assay. Results: The frequencies of the rs3794087 genotypes and alleles were similar in patients with migraine and controls, and were unrelated with the age of onset of migraine, gender, presence or absence of aura, or family history of migraine Conclusion: rs3794087 genotype and allelic variants were not related with the risk for migraine in Caucasian Spanish people. (C) 2013 Elsevier B.V. All rights reserved.
Decreased EAAT2 protein expression in the essential tremor cerebellar cortex
ACTA NEUROPATHOLOGICA COMMUNICATIONS
Authors: Lee, Michelle; Cheng, Melody M.; Lin, Chi-Ying; Louis, Elan D.; Faust, Phyllis L.; Kuo, Sheng-Han
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.