Analysis of oxysterols and cholesterol in prefrontal cortex of suicides.
Brain oxysterol levels, which are enzymatic oxidation products of cholesterol (Chl), have been proposed to reflect the dynamic process of physiological synapse maintenance and repair of nerve terminals within the central nervous system (CNS), due to the turnover of membrane Chl. Modifications of oxysterols have important implications in neurological conditions, especially in neurodegenerative and psychiatric disorders in which alterations of synaptic plasticity or cell signalling are implicated, such as depression. Oxysterols can diffuse across the blood-brain barrier and have been hypothesized to provide a mechanism by which the brain can eliminate excess Chl to maintain a steady state. Relations of 24-hydroxycholesterol (24OH) and 27-hydroxycholesterol (27OH) specifically may provide a depiction of CNS Chl homeostasis. Thus, the objective of this study was to integrate oxysterol measures and gene expression measures in an effort to identify how they may relate to depression and suicide. Using post-mortem human prefrontal cortex tissue, quantification of metabolites by GC-MS and gene expression by qRT-PCR were performed with the aim to provide a characterization of enzymatic oxidative Chl homeostasis. Results show a significant increase in 24OH, which suggests a higher turnover of Chl to 24OH in the prefrontal cortex of suicide cases. An increase in 24OH may, in combination with liver-X receptor activation, explain the observed reduction of low central and peripheral Chl in suicide and would have implications for synapse maintenance and loss in the neuropathology of depression and suicide.
Department of Human Genetics, McGill University, Montreal, QC, Canada.
Erika
E
Freemantle
Gary Gang
GG
Chen
Cristiana
C
Cruceanu
Naguib
N
Mechawar
Gustavo
G
Turecki
D000328:Adult; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013405:Suicide
D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; D002784:Cholesterol; D006899:Mixed Function Oxygenases