Expression of POU-domain transcription factor, Oct-6, in schizophrenia, bipolar disorder and major depression

Abstract

Background: The POU-domain transcription factor Oct-6 has been reported to be differentially expressed between schizophrenic and control post-mortem brains. In this study, we attempted to replicate this finding and to discover whether Oct-6 was also dysregulated in bipolar disorder and major depression.

Methods: Oct-6 mRNA and protein expression were determined by in-situ hybridization and immunohistochemistry respectively in sections of post-mortem brain.

Results: We did not observe any differences in Oct-6 expression between any of the groups under study. Oct-6 mRNA and protein was identically expressed in the hippocampal and cortical regions of most specimens in all groups, including controls.

Conclusion: Oct-6 is, therefore, unlikely to be a specific marker for any psychological disorder; rather its expression in controls suggests that it is normally expressed in most adult brains.

Figure 1

Oct-6 Immunoreactivity in Paraffin-embedded Tissue from Control, Schizophrenic, Bipolar Disorder and Major Depression. Oct-6 immunoreactivity was observed in hippocampal subfields CA4, CA3 and CA1 in controls (CON A – C), schizophrenics (SCH D – F), bipolar disorder (BP G – I) and major depression (MD J – L). Oct-6 immunoreactivity was observed in groups in a cytoplasmic/perinuclear fashion (arrowheads). Oct-6-positive cells had the morphological appearance of pyramidal neurons. Immunoreactivity is visible in the apical dendrites of some neurons (arrows in (H) and (K)) Scale bars = 50 μm

Figure 2

Oct-6 Immunoreactivity in the Cerebral Cortex. Oct-6 immunoreactivity in the cerebral cortex of a schizophrenic patient. Staining was observed in a layer-specific pattern restricted to layers II/III and V (B) seen at higher magnification in (A) & (C). Oct-6-positive cells had the morphological characteristics of pyramidal neurones. In general, POU3F1 immunoreactivity was dispersed throughout the cell (asterisks in A), though some did have the cytoplasmic/perinuclear localization noted in the hippocampus (arrowheads in A). Immunoreactivity was also observed in the apical dendrites (arrows). Cells in layer V (C) appeared considerably smaller than those in layer II/III (A). A similar cortical expression was observed in all groups. Scale bars: (B) = 200 μm (A & C) = 50 μm

Figure 3

Oct-6 Immunoreactivity in Fresh-frozen Tissue from Control, Schizophrenic, Bipolar Disorder and Major Depression. Oct-6 immunoreactivity was observed in all groups (CON A – C and CON (2) D- F), schizophrenics (SCH G – I), bipolar disorder (BP J – L) and major depression (MD M – O) and did not differ between groups or in comparison to controls. Oct-6-positive cells had the morphological appearance of pyramidal neurons. In the CA4 and CA3 regions immunoreactivity generally took on a nuclear localization (arrowheads) thought in some cases a more dispersed pattern of expression was noted (asterisks). Oct-6 immunoreactivity was also noted the apical dendrites of some cells (arrows). Though staining was robust throughout, it appeared stronger in the CA1 region (C, F, I, L & O), in all cases Oct-6 immunoreactivity in the CA1 was nuclear. Scale bars = 50 μm

Figure 4

Oct-6 mRNA expression in Control, Schizophrenic, Bipolar Disorder and Major Depression Patients. Oct-6 mRNA expression (arrowheads) was observed in hippocampal fields CA4 (A, E, H & K), CA3 (B, F, I & L) and CA1 (C, G, J and M) in all groups including controls (controls = CON, schizophrenics = SCH bipolar disorder = BP and major depression = MD). No qualitative differences were noted in hybridization signal between different regions or groups. Oct-6 mRNA was observed in a layer-specific pattern in the cortical layers II/III and V (D). Scale bars: (D) = 500 μm, all others = 50 μm