Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder.
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.
Department of Psychiatry and Human Behavior, USA. Electronic address: grajkowska@umc.edu.
Grazyna
G
Rajkowska
Department of Psychiatry and Human Behavior, USA. Electronic address: gmahajan@umc.edu.
Gouri
G
Mahajan
Department of Psychiatry and Human Behavior, USA. Electronic address: dorotamaciag@yahoo.com.
Dorota
D
Maciag
Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 E. Clark St., Vermillion, SD, 57069, USA. Electronic address: Monica.Sathyanesan@usd.edu.
Monica
M
Sathyanesan
Department of Psychiatry and Human Behavior, USA. Electronic address: alawarik@yahoo.ca.
Abiye H
AH
Iyo
Department of Psychiatry and Human Behavior, USA. Electronic address: mmoulana@umc.edu.
Mohadetheh
M
Moulana
Department of Pathology, University of Mississippi Medical Center, 2500 North State St., Jackson, MS, 39216, USA. Electronic address: pkyle@umc.edu.
Patrick B
PB
Kyle
Department of Psychiatry and Human Behavior, USA.
William L
WL
Woolverton
Department of Psychiatry and Human Behavior, USA. Electronic address: jmiguel-hidalgo@umc.edu.
Jose Javier
JJ
Miguel-Hidalgo
Department of Psychiatry and Human Behavior, USA; Department of Psychiatry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA. Electronic address: cstockmeier@umc.edu.
Craig A
CA
Stockmeier
Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 E. Clark St., Vermillion, SD, 57069, USA. Electronic address: Samuel.Sathyanesan@usd.edu.
Samuel S
SS
Newton
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism*; D055815:Young Adult
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D051792:Basic Helix-Loop-Helix Proteins; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C405707:OLIG1 protein, human; C472930:PLP1 protein, human
CNPase; MOG; Myelin; OLIG1; PLP1; Postmortem