title: Increased nuclear Olig1-expression in the pregenual anterior cingulate white matter of patients with major depression: a regenerative attempt to compensate oligodendrocyte loss?
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.
authors.affiliation: Department of Psychiatry, University of Magdeburg, Magdeburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mosebach
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gos
authors.forename: Kolja
authors.initials: K
authors.lastname: Schiltz
authors.forename: Linda
authors.initials: L
authors.lastname: Schoeneck
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Susan
authors.initials: S
authors.lastname: Müller
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Schroeter
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D017397:Prefrontal Cortex / Q000473:pathology; D012559:Schizophrenia / Q000473:pathology
chemical_list: D000928:Antidepressive Agents; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; C499048:MBP protein, human; C405707:OLIG1 protein, human