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Increased nuclear Olig1-expression in the pregenual anterior cingulate white matter of patients with major depression: A regenerative attempt to compensate oligodendrocyte loss?

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Schroeter,  Matthias L.
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

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Citation

Mosebach, J., Keilhoff, G., Gos, T., Schiltz, K., Schoeneck, L., Dobrowolny, H., et al. (2013). Increased nuclear Olig1-expression in the pregenual anterior cingulate white matter of patients with major depression: A regenerative attempt to compensate oligodendrocyte loss? Journal of Psychiatric Research, 47(8), 1069-1079. doi:10.1016/j.jpsychires.2013.03.018.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-F0E0-2
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.