Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder

Grazyna Rajkowska, Gouri Mahajan, Dorota Maciag, Monica Sathyanesan, Abiye H. Iyo, Mohadetheh Moulana, Patrick B. Kyle, William L. Woolverton, Jose Javier Miguel-Hidalgo, Craig A. Stockmeier, Samuel Sathyanesan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

White matter disturbance in the ventral prefrontal cortex (vPFC) in major depressive disorder (MDD) has been noted with diffusion tensor imaging (DTI). However, the cellular and molecular pathology of prefrontal white matter in MDD and potential influence of antidepressant medications is not fully understood. Oligodendrocyte morphometry and myelin-related mRNA and protein expression was examined in the white matter of the vPFC in MDD. Sections of deep and gyral white matter from the vPFC were collected from 20 subjects with MDD and 16 control subjects. Density and size of CNPase-immunoreactive (-IR) oligodendrocytes were estimated using 3-dimensional cell counting. While neither density nor soma size of oligodendrocytes was significantly affected in deep white matter, soma size was significantly decreased in the gyral white matter in MDD. In rhesus monkeys treated chronically with fluoxetine there was no significant effect on oligodendrocyte morphometry. Using quantitative RT-PCR to measure oligodendrocyte-related mRNA for CNPase, PLP1, MBP, MOG, MOBP, Olig1 and Olig2, in MDD there was a significantly reduced expression of PLP1 mRNA (which positively correlated with smaller sizes) and increased expression of mRNA for CNPase, OLIG1 and MOG. The expression of CNPase protein was significantly decreased in MDD. Altered expression of four myelin genes and CNPase protein suggests a mechanism for the degeneration of cortical axons and dysfunctional maturation of oligodendrocytes in MDD. The change in oligodendrocyte morphology in gyral white matter may parallel altered axonal integrity as revealed by DTI.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalJournal of Psychiatric Research
Volume65
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Oligodendroglia
Major Depressive Disorder
2',3'-Cyclic-Nucleotide Phosphodiesterases
Myelin Sheath
Messenger RNA
Prefrontal Cortex
Diffusion Tensor Imaging
Carisoprodol
Proteins
Molecular Pathology
White Matter
Morphometry
Fluoxetine
Macaca mulatta
Antidepressive Agents
Axons
Polymerase Chain Reaction

Keywords

  • CNPase
  • MOG
  • Myelin
  • OLIG1
  • PLP1
  • Postmortem

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder. / Rajkowska, Grazyna; Mahajan, Gouri; Maciag, Dorota; Sathyanesan, Monica; Iyo, Abiye H.; Moulana, Mohadetheh; Kyle, Patrick B.; Woolverton, William L.; Miguel-Hidalgo, Jose Javier; Stockmeier, Craig A.; Sathyanesan, Samuel.

In: Journal of Psychiatric Research, Vol. 65, 01.06.2015, p. 53-62.

Research output: Contribution to journalArticle

Rajkowska, G, Mahajan, G, Maciag, D, Sathyanesan, M, Iyo, AH, Moulana, M, Kyle, PB, Woolverton, WL, Miguel-Hidalgo, JJ, Stockmeier, CA & Sathyanesan, S 2015, 'Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder', Journal of Psychiatric Research, vol. 65, pp. 53-62. https://doi.org/10.1016/j.jpsychires.2015.04.010
Rajkowska, Grazyna ; Mahajan, Gouri ; Maciag, Dorota ; Sathyanesan, Monica ; Iyo, Abiye H. ; Moulana, Mohadetheh ; Kyle, Patrick B. ; Woolverton, William L. ; Miguel-Hidalgo, Jose Javier ; Stockmeier, Craig A. ; Sathyanesan, Samuel. / Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder. In: Journal of Psychiatric Research. 2015 ; Vol. 65. pp. 53-62.
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abstract = "White matter disturbance in the ventral prefrontal cortex (vPFC) in major depressive disorder (MDD) has been noted with diffusion tensor imaging (DTI). However, the cellular and molecular pathology of prefrontal white matter in MDD and potential influence of antidepressant medications is not fully understood. Oligodendrocyte morphometry and myelin-related mRNA and protein expression was examined in the white matter of the vPFC in MDD. Sections of deep and gyral white matter from the vPFC were collected from 20 subjects with MDD and 16 control subjects. Density and size of CNPase-immunoreactive (-IR) oligodendrocytes were estimated using 3-dimensional cell counting. While neither density nor soma size of oligodendrocytes was significantly affected in deep white matter, soma size was significantly decreased in the gyral white matter in MDD. In rhesus monkeys treated chronically with fluoxetine there was no significant effect on oligodendrocyte morphometry. Using quantitative RT-PCR to measure oligodendrocyte-related mRNA for CNPase, PLP1, MBP, MOG, MOBP, Olig1 and Olig2, in MDD there was a significantly reduced expression of PLP1 mRNA (which positively correlated with smaller sizes) and increased expression of mRNA for CNPase, OLIG1 and MOG. The expression of CNPase protein was significantly decreased in MDD. Altered expression of four myelin genes and CNPase protein suggests a mechanism for the degeneration of cortical axons and dysfunctional maturation of oligodendrocytes in MDD. The change in oligodendrocyte morphology in gyral white matter may parallel altered axonal integrity as revealed by DTI.",
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AU - Iyo, Abiye H.

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