title: Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University , Düsseldorf , Germany.
authors.forename: Martina Von
authors.initials: MV
authors.lastname: Wilmsdorff
authors.forename: Carolin
authors.initials: C
authors.lastname: Blaich
authors.forename: Mathias
authors.initials: M
authors.lastname: Zink
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.forename: Manfred
authors.initials: M
authors.lastname: Bauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulze
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider-Axmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
mesh_terms: D000368:Aged; D000483:Alleles; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003024:Clozapine / Q000627:therapeutic use; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis / Q000235:genetics*; D050580:Excitatory Amino Acid Transporter 3 / Q000096:biosynthesis / Q000235:genetics*; D050581:Excitatory Amino Acid Transporter 4 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; C094131:NRG1 protein, human; D020890:Neuregulin-1; D003024:Clozapine; D006220:Haloperidol