Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder
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Published on: November 27, 2019
Grazyna Rajkowska1, Gouri Mahajan1, Dorota Maciag1
1Department of Psychiatry and Human Behavior, USA.
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.
Insights
Major depressive disorder (MDD) shows altered oligodendrocyte size and myelin gene expression in the ventral prefrontal cortex (vPFC). These findings suggest a cellular basis for white matter changes in MDD.
Area of Science:
- Neuroscience
- Cellular Biology
- Molecular Psychiatry
Background:
- White matter disturbances in the ventral prefrontal cortex (vPFC) are observed in major depressive disorder (MDD) using diffusion tensor imaging (DTI).
- The precise cellular and molecular pathology of prefrontal white matter in MDD, and the impact of antidepressant medications, remain incompletely understood.
Purpose of the Study:
- To investigate oligodendrocyte morphometry and myelin-related gene and protein expression in the vPFC white matter of individuals with MDD.
- To explore potential correlations between oligodendrocyte changes, myelin gene expression, and DTI findings in MDD.
Main Methods:
- Oligodendrocyte density and soma size were quantified using 3D cell counting in deep and gyral vPFC white matter from MDD and control subjects.
- Quantitative RT-PCR was employed to measure mRNA expression of myelin-related genes (CNPase, PLP1, MBP, MOG, MOBP, Olig1, Olig2).
- CNPase protein expression was assessed, and oligodendrocyte morphometry was examined in rhesus monkeys treated with fluoxetine.
Main Results:
- Oligodendrocyte soma size was significantly reduced in the gyral white matter of MDD subjects compared to controls.
- MDD was associated with significantly reduced PLP1 mRNA expression and increased expression of CNPase, OLIG1, and MOG mRNA.
- CNPase protein expression was significantly decreased in MDD subjects, while fluoxetine treatment did not affect oligodendrocyte morphometry in monkeys.
Conclusions:
- Altered expression of myelin genes and CNPase protein in the vPFC suggests a mechanism for axonal degeneration and impaired oligodendrocyte maturation in MDD.
- Changes in oligodendrocyte morphology in gyral white matter may correspond with altered axonal integrity observed via DTI in MDD.
- These cellular and molecular alterations provide insights into the neuropathology of white matter in major depressive disorder.
