Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment

Martina Von Wilmsdorff, Carolin Blaich, Mathias Zink, Jens Treutlein, Manfred Bauer, Thomas Schulze, Thomas Schneider-Axmann, Oliver Gruber, Marcella Rietschel, Andrea Schmitt, Peter Falkai

Research output: Contribution to journalArticle

Abstract

Objectives. The glutamatergic hypothesis of schizophrenia proposes alterations of excitatory amino acid transporters (solute carrier family, SLCs) expression and cerebellar dysfunctions. The influence of the neuregulin-1 (NRG1) risk genotype or effects of antipsychotics on expression of EAATs are unknown. Methods. We compared post-mortem samples from the cerebellar hemispheres and vermis of 10 schizophrenia patients with nine normal subjects by investigating gene expression of SLC1A3, SLC1A1 and SLC1A6 by in-situ hybridization. We further assessed the allelic composition regarding the polymorphism rs35753505 (SNP8NRG221533) near the NRG1 gene. To control for effects due to antipsychotic treatment, we chronically treated rats with the antipsychotics haloperidol or clozapine and assessed gene expression of SLCs. Results. Schizophrenia patients showed increased expression of SLC1A3 in the molecular layer of the vermis. Individuals carrying at least one C allele of rs35753505 (SNP8NRG221533) showed decreased expression of SLC1A6 in the molecular layer of both hemispheres, compared to individuals homozygous for the T allele. The animal model revealed suppression of SLC1A6 by clozapine. Conclusions. Increased SLC1A3 expression indicates facilitated transport and may result in reduced glutamate neurotransmission. Decreased SLC1A6 expression in NRG1 risk variant may be an adaptive effect to restore glutamate signalling, but treatment effects cannot be excluded.

Original languageEnglish (US)
Pages (from-to)490-499
Number of pages10
JournalWorld Journal of Biological Psychiatry
Volume14
Issue number7
DOIs
Publication statusPublished - Sep 2013
Externally publishedYes

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Keywords

  • Antipsychotics
  • Cerebellum
  • Gene expression
  • Glutamate transporters
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry
  • Psychiatry and Mental health

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