title: Increased mRNA expression of peripheral glial cell markers in bipolar disorder: The effect of long-term lithium treatment.
abstract: Neuroinflammation, with microglial activation as an important element, plays a role in the pathogenesis of bipolar disorder (BD). Also, in mood disorders, pathological changes have been demonstrated in macroglial cells, such as astrocyctes and oligodendrocytes. Postmortem brain studies of BD patients to assess glial cells, such as astrocytes and oligodendrocytes and their markers such as glial fibrillary acidic protein (GFAP), Olig1 and Olig2, produced controversial results. On the other hand, investigation of these markers in the peripheral blood of such patients has not been performed so far. In this study, we examined the mRNA levels of GFAP, Olig1 and Olig2, in the peripheral blood of three groups: 15 BD subjects with a duration of illness at least 10 years (mean 20±9 years) but never treated with lithium, 15 subjects with BD treated continuously with lithium for 8-40 years (mean 16±8 years), and 15 control subjects. The groups were age-and sex-matched. Expression of mRNA markers was measured by real-time quantitative reverse transcription PCR (RQ-PCR). We observed increased mRNA levels of the Olig1 and Olig 2 glial markers studied in the BD patients not taking lithium, compared with the control subjects and increased mRNA level of GFAP, compared with lithium-treated patients. In the lithium-treated BD patients GFAP and Olig1 expression was at similar levels to that in the control group. However, Olig 2 expression was even higher than in the BD patients not taking lithium. The possible mechanisms concerning the higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. The beneficial effect of lithium may be related to its anti-inflammatory properties.
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Ferensztajn-Rochowiak
authors.affiliation: Department of Physiology, Pomeranian University of Medicine, Szczecin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarnowski
authors.affiliation: Department of Psychiatry, Pomeranian University of Medicine, Szczecin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Samochowiec
authors.affiliation: Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Department of Physiology, Pomeranian University of Medicine, Szczecin, Poland; Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: janusz.rybakowski@gmail.com.
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000097:blood; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2 / Q000097:blood; D012333:RNA, Messenger / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018020:Lithium Compounds; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; C405707:OLIG1 protein, human; C405708:OLIG2 protein, human
keywords: Astrocytes; Bipolar disorder; Glial fibrillary acidic protein (GFAP); Lithium; Oligodendrocyte lineage genes (Olig); Oligodendrocytes