Exploratory study of the dysregulation of age-related changes in neural/glial antigen 2 and neuroinflammation markers in individuals with major depression

Abstract

Aging involves the alteration of the central nervous system myelin, which is produced by oligodendrocytes. These cells originate from oligodendrocyte precursor [neural/glial antigen 2 (NG2)] cells, which are influenced by neuroinflammatory processes. Neuroinflammatory activity contributes to accelerated aging in individuals with mental illnesses such as major depressive disorder (MDD). This study was conducted to better understand the anti- and pro-neuroinflammatory changes associated with NG2 cells in aging individuals with MDD. Human postmortem dorsolateral prefrontal cortex samples were obtained from adults with MDD and normal controls (NCs) of different ages. Western blotting was performed to measure the protein levels of the oligodendrocyte progenitor cell marker NG2, the inflammatory markers interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor (HGF), and the anti-inflammatory neuronal viability marker B-cell lymphoma 2 (Bcl-2). Age-related changes in these markers were examined by simple linear regression. In NCs, the levels of NG2 and HGF increased linearly with age (p = 0.04 and p = 0.02, respectively), and the Bcl-2 level tended to follow the same trend (p = 0.08). The IL-1β and TNF-α levels were not significantly associated with age in NCs (p = 0.96 and p = 0.67, respectively). In the MDD group, a linear relationship with age was observed for the HGF level (p = 0.03) but not the NG2 (p = 0.23) or Bcl-2 (p = 0.92) level. Trends toward significant positive linear relationships with age were observed for the levels of IL-1β (p = 0.06) and TNF-α (p = 0.08). Our data suggest that brain aging is advanced in individuals with MDD in part due to increased neuroinflammation and reduced pro-survival protein levels and myelination potential.