Excitatory Amino acid transporter expression in the essential tremor dentate nucleus and cerebellar cortex: A postmortem study.
Genome-wide association studies have revealed a link between essential tremor (ET) and the gene SLC1A2, which encodes excitatory amino acid transporter type 2 (EAAT2). We explored EAAT biology in ET by quantifying EAAT2 and EAAT1 levels in the cerebellar dentate nucleus, and expanded our prior analysis of EAAT2 levels in the cerebellar cortex.



To quantify EAAT2 and EAAT1 levels in the cerebellar dentate nucleus and cerebellar cortex of ET cases vs.







We used immunohistochemistry to quantify EAAT2 and EAAT1 levels in the dentate nucleus of a discovery cohort of 16 ET cases and 16 controls. Furthermore, we quantified EAAT2 levels in the dentate nucleus in a replicate cohort (61 ET cases, 25 controls). Cortical EAAT2 levels in all 77 ET cases and 41 controls were quantified.



In the discovery cohort, dentate EAAT2 levels were 1.5-fold higher in 16 ET cases vs. 16 controls (p = 0.007), but EAAT1 levels did not differ significantly (p = 0.279). Dentate EAAT2 levels were 1.3-fold higher in 61 ET cases vs. 25 controls in the replicate cohort (p = 0.022). Cerebellar cortical EAAT2 levels were 20% and 40% lower in ET cases vs. controls in the discovery and the replicate cohorts (respective p values = 0.045 and < 0.001).



EAAT2 expression is enhanced in the ET dentate nucleus, in contrast to differentially reduced EAAT2 levels in the ET cerebellar cortex, which might reflect a compensatory mechanism to maintain excitation-inhibition balance in cerebellar nuclei.
Department of Basic and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, China; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Jie
J
Wang
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
Geoffrey C
GC
Kelly
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
William J
WJ
Tate
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Yong-Shi
YS
Li
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
Michelle
M
Lee
Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA.
Jesus
J
Gutierrez
Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA; Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA; Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA.
Elan D
ED
Louis
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
Phyllis L
PL
Faust
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: sk3295@columbia.edu.
Sheng-Han
SH
Kuo
D000368:Aged; D000369:Aged, 80 and over; D002525:Cerebellar Cortex / Q000378:metabolism*; D002529:Cerebellar Nuclei / Q000378:metabolism*; D003933:Diagnosis; D020329:Essential Tremor / Q000473:pathology*; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D005970:Glutamate Synthase / Q000378:metabolism; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018709:Statistics, Nonparametric
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; D005970:Glutamate Synthase
Cerebellum; EAAT2; Essential tremor; Excitotoxicitiy; GFAP; Neurodegenerative