Differential expression of genes encoding neuronal ion-channel subunits in major depression, bipolar disorder and schizophrenia: Implications for pathophysiology

Bella Smolin, Rachel Karry, Shunit Gal-Ben-Ari, Dorit Ben-Shachar

Research output: Contribution to journalArticlepeer-review

Abstract

Evidence concerning ion-channel abnormalities in the pathophysiology of common psychiatric disorders is still limited. Given the significance of ion channels in neuronal activity, neurotransmission and neuronal plasticity we hypothesized that the expression patterns of genes encoding different ion channels may be altered in schizophrenia, bipolar and unipolar disorders. Frozen samples of striatum including the nucleus accumbens (Str-NAc) and the lateral cerebellar hemisphere of 60 brains from depressed (MDD), bipolar (BD), schizophrenic and normal subjects, obtained from the Stanley Foundation Brain Collection, were assayed. mRNA of 72 different ion-channel subunits were determined by qRTa-PCR and alteration in four genes were verified by immunoblotting. In the Str-NAc the prominent change was observed in the MDD group, in which there was a significant up-regulation in genes encoding voltage-gated potassium-channel subunits. However, in the lateral cerebellar hemisphere (cerebellum), the main change was observed in schizophrenia specimens, as multiple genes encoding various ion-channel subunits were significantly down-regulated. The impaired expression of genes encoding ion channels demonstrates a disease-related neuroanatomical pattern. The alterations observed in Str-NAc of MDD may imply electrical hypo-activity of this region that could be of relevance to MDD symptoms and treatment. The robust unidirectional alteration of both excitatory and inhibitory ion channels in the cerebellum may suggests cerebellar general hypo-transcriptional activity in schizophrenia.

Original languageEnglish
Pages (from-to)869-882
Number of pages14
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number7
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Bipolar disorder
  • human post-mortem brain specimens
  • ion channel gene expression
  • major depression
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Pharmacology

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