title: Differentiation of oligodendrocyte precursors is impaired in the prefrontal cortex in schizophrenia.
abstract: The pathophysiology of schizophrenia involves disturbances of information processing across brain regions, possibly reflecting, at least in part, a disruption in the underlying axonal connectivity. This disruption is thought to be a consequence of the pathology of myelin ensheathment, the integrity of which is tightly regulated by oligodendrocytes. In order to gain insight into the possible neurobiological mechanisms of myelin deficit, we determined the messenger RNA (mRNA) expression profile of laser captured cells that were immunoreactive for 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), a marker for oligodendrocyte progenitor cells (OPCs) in addition to differentiating and myelinating oligodendrocytes, in the white matter of the prefrontal cortex in schizophrenia subjects. Our findings pointed to the hypothesis that OPC differentiation might be impaired in schizophrenia. To address this hypothesis, we quantified cells that were immunoreactive for neural/glial antigen 2 (NG2), a selective marker for OPCs, and those that were immunoreactive for oligodendrocyte transcription factor 2 (OLIG2), an oligodendrocyte lineage marker that is expressed by OPCs and maturing oligodendrocytes. We found that the density of NG2-immunoreactive cells was unaltered, but the density of OLIG2-immunoreactive cells was significantly decreased in subjects with schizophrenia, consistent with the notion that OPC differentiation impairment may contribute to oligodendrocyte disturbances and thereby myelin deficits in schizophrenia.
authors.affiliation: Laboratory for Cellular Neuropathology, McLean Hospital, Belmont, MA 02478, United States; Division of Basic Neuroscience, McLean Hospital, Belmont, MA 02478, United States.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Mauney
authors.affiliation: Laboratory for Cellular Neuropathology, McLean Hospital, Belmont, MA 02478, United States; Division of Basic Neuroscience, McLean Hospital, Belmont, MA 02478, United States.
authors.forename: Charmaine Y
authors.initials: CY
authors.lastname: Pietersen
authors.affiliation: Division of Basic Neuroscience, McLean Hospital, Belmont, MA 02478, United States; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Kai-C
authors.initials: KC
authors.lastname: Sonntag
authors.affiliation: Laboratory for Cellular Neuropathology, McLean Hospital, Belmont, MA 02478, United States; Division of Basic Neuroscience, McLean Hospital, Belmont, MA 02478, United States; Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, United States. Electronic address: wwoo@hms.harvard.edu.
authors.forename: Tsung-Ung W
authors.initials: TW
authors.lastname: Woo
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000941:Antigens / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000473:pathology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D012333:RNA, Messenger; D000099216:Chondroitin Sulfate Proteoglycan 4; C405708:OLIG2 protein, human