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J Psychiatr Res ; 47(8): 1069-79, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23615187

ABSTRACT

BACKGROUND: Structural and functional oligodendrocyte deficits as well as impaired myelin integrity have been described in affective disorders and schizophrenia, and may disturb the connectivity between disease-relevant brain regions. Olig1, an oligodendroglial transcription factor, might be important in this context, but has not been systematically studied so far. METHODS: Nissl- and Olig1-stained oligodendrocytes were quantified in the pregenual anterior cingulate (pACC)/dorsolateral prefrontal cortex (DLPFC), and adjacent white matter of patients with major depressive disorder (MDD, n = 9), bipolar disorder (BD, n = 8), schizophrenia (SZ, n = 13), and matched controls (n = 16). Potential downstream effects of increased Olig1-expression were analyzed. Antidepressant drug effects on Olig1-expression were further explored in OLN-93 oligodendrocyte cultures. RESULTS: Nissl-stainings of both white matter regions showed a 19-27% reduction of total oligodendrocyte densities in MDD and BD, but not in SZ. In contrast, nuclear Olig1-immunoreactivity was elevated in MDD in the pACC-adjacent white matter (left: p = 0.008; right: p = 0.018); this effect tended to increase with antidepressant dosage (r = 0.631, p = 0.069). This reactive increase of Olig1 was confirmed by partly dose-dependent effects of imipramine and amitriptyline in oligodendrocyte cultures. Correspondingly, MBP expression in the pACC-adjacent white matter tended to increase with antidepressant dosage (r = 0.637, p = 0.065). Other tested brain regions showed no diagnosis-dependent differences regarding Olig1-immunoreactivity. CONCLUSIONS: Since nuclear Olig1-expression marks oligodendrocyte precursor cells, its increased expression along with reduced total oligodendrocyte densities (Nissl-stained) in the pACC-adjacent white matter of MDD patients might indicate a (putatively medication-boosted) regenerative attempt to compensate oligodendrocyte loss.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Depressive Disorder, Major/pathology , Gyrus Cinguli/pathology , Nerve Fibers, Myelinated/metabolism , Nerve Tissue Proteins/metabolism , Oligodendroglia/metabolism , Adult , Aged , Analysis of Variance , Antidepressive Agents/therapeutic use , Bromodeoxyuridine/metabolism , Cell Survival/drug effects , Cells, Cultured , Depressive Disorder, Major/drug therapy , Female , Glial Fibrillary Acidic Protein/metabolism , Gyrus Cinguli/metabolism , Humans , Male , Middle Aged , Myelin Basic Protein/metabolism , Oligodendroglia/pathology , Prefrontal Cortex/pathology , Schizophrenia/pathology
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