Differential expression of genes encoding neuronal ion-channel subunits in major depression, bipolar disorder and schizophrenia: implications for pathophysiology.
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 qRT-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.
Department of Internal Medicine, Rambam Medical Center, B Rappaport Faculty of Medicine and B Rappaport Research Institute, Technion, Haifa Israel.
Bella
B
Smolin
Rachel
R
Karry
Shunit
S
Gal-Ben-Ari
Dorit
D
Ben-Shachar
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018118:Chloride Channels; D007473:Ion Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D015222:Sodium Channels