4.6 Article

Distinct Expression Pattern of Epigenetic Machinery Genes in Blood Leucocytes and Brain Cortex of Depressive Patients

Journal

MOLECULAR NEUROBIOLOGY
Volume 56, Issue 7, Pages 4697-4707

Publisher

SPRINGER
DOI: 10.1007/s12035-018-1406-0

Keywords

Depression; Epigenesis; Genetic; Brain; Leucocytes; Gene expression

Categories

Funding

  1. University Hospital of Dijon (Hospital Protocol of Clinical Research) [2009-A01146-51]
  2. Le Vinatier Hospital

Ask authors/readers for more resources

In major depressive disorder (MDD), altered gene expression in brain cortex and blood leucocytes may be due to aberrant expression of epigenetic machinery coding genes. Here, we explore the expression of these genes both at the central and peripheral levels. Using real-time quantitative PCR technique, we first measured expression levels of genes encoding DNA and histone modifying enzymes in the dorsolateral prefrontal cortex (DLPFC) and cingulate cortex (CC) of MDD patients (n = 24) and healthy controls (n = 12). For each brain structure, transcripts levels were compared between subject groups. In an exploratory analysis, we then compared the candidate gene expressions between a subgroup of MDD patients with psychotic characteristics (n = 13) and the group of healthy subjects (n = 12). Finally, we compared transcript levels of the candidate genes in blood leucocytes between separate samples ofMDD patients (n = 17) and healthy controls (n = 16). In brain and blood leucocytes of MDD patients, we identified an overexpression of genes encoding enzymes which transfer repressive transcriptional marks: HDAC4-5-6-8 and DNMT3B in the DLPFC, HDAC2 in the CC and blood leucocytes. In the DLPFC of patients with psychotic characteristics, two genes (KAT2A and UBE2A) were additionally overexpressed suggesting a shift to a more transcriptionally permissive conformation of chromatin. Aberrant activation of epigenetic repressive systems may be involved in MDD pathogenesis both in brain tissue and blood leucocytes.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available