Excitatory Amino acid transporter expression in the essential tremor dentate nucleus and cerebellar cortex: A postmortem study

Parkinsonism Relat Disord. 2016 Nov:32:87-93. doi: 10.1016/j.parkreldis.2016.09.003. Epub 2016 Sep 6.

Abstract

Background: 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.

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

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Cerebellum; EAAT2; Essential tremor; Excitotoxicitiy; GFAP; Neurodegenerative.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebellar Cortex / metabolism*
  • Cerebellar Nuclei / metabolism*
  • Diagnosis
  • Essential Tremor / pathology*
  • Excitatory Amino Acid Transporter 1 / genetics
  • Excitatory Amino Acid Transporter 1 / metabolism*
  • Excitatory Amino Acid Transporter 2
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamate Plasma Membrane Transport Proteins / genetics*
  • Glutamate Plasma Membrane Transport Proteins / metabolism
  • Glutamate Synthase / metabolism
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Statistics, Nonparametric

Substances

  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • Glial Fibrillary Acidic Protein
  • Glutamate Plasma Membrane Transport Proteins
  • SLC1A2 protein, human
  • SLC1A3 protein, human
  • Glutamate Synthase