Chunk #13 — 5. Inflammasome is a key mediator of stress, depression and comorbid illnesses — 5.2. Inflammatory cytokines and dysfunction of the HPA axis
Sustained levels of glucocorticoids can cause atrophy of pyramidal neurons in the hippocampus and medial prefrontal cortex (mPFC), and thereby contribute to depressive symptoms (Sapolsky et al., 2000; Wellman, 2001). These effects could be due to excitotoxicity (Nestler et al., 2002; Sapolsky et al., 2000; Woolley et al., 1990), decreased BDNF expression (Smith et al., 1995; Schaaf et al. 2000), and/or decreased neurogenesis in the adult hippocampus (Chaouloff and Groc, 2011; Muller and Schwarz, 2007; Nestler et al., 2002; Tse et al., 2011). Loss of hippocampal function and negative feedback could also contribute to over activation of the HPA axis (Zunszain et al., 2012).
