Elevated Delta-6 desaturase (FADS2) gene expression in the prefrontal cortex of patients with bipolar disorder.
Although evidence suggests that a dysregulation in polyunsaturated fatty acid (PUFA) homeostasis may contribute to the pathoetiology of bipolar disorder (BD), there is currently nothing known about the expression of genes that mediate long-chain PUFA biosynthesis in BD patients. In the present study we determined FADS1 (Δ5 desaturase), FADS2 (Δ6 desaturase), HELO1 [ELOVL5] (elongase), PEX19 (peroxisome), and SCD (stearoyl-CoA desaturase [Δ9 desaturase]) mRNA expression in the postmortem prefrontal cortex of non-psychiatric controls (n = 12) and BD patients (n = 12) by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Changes in the activities of corresponding enzyme products were estimated from fatty acid product: precursor ratios. After correcting for multiple comparisons, FADS2 mRNA expression was significantly greater in BD patients relative to controls (+27%, p = 0.004). Indices of Δ6 desaturase activity, including 20:4/18:2 (+18%, p = 0.15) and 20:3/18:2 (+12%, p = 0.25) ratios, were numerically, but not significantly, greater in BD patients relative to controls. There were no significant group differences in FADS1 (+17%, p = 0.32), HELO1 (+4%, p = 0.81), PEX19 (-2%, p = 0.91), and SCD (+4%, p = 0.85) mRNA expression, or indices of Δ5 desaturase (+5%, 0.59), elongase (+3%, p = 0.62), and stearoyl-CoA desaturase (-11%, p = 0.10) activities. These preliminary findings demonstrate that FADS2 mRNA expression is significantly and selectively elevated in the prefrontal cortex of BD patients, and may contribute to dysregulated central PUFA biosynthesis and pro-inflammatory signaling implicated in the pathophysiology of BD.
Liu
Yanhong
Y
Department of Psychiatry, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, 260 Stetson Street, Suite 3306, Cincinnati, OH 45219, USA.
McNamara
Robert K
RK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000473:pathology* / Q000503:physiopathology*; D002849:Chromatography, Gas; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
D000090943:Delta-5 Fatty Acid Desaturase; D012333:RNA, Messenger; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human