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. Author manuscript; available in PMC: 2013 Jan 1.
Published in final edited form as: Exp Neurol. 2011 Oct 6;233(1):79–86. doi: 10.1016/j.expneurol.2011.09.035

Figure 1. Molecular and cellular effects of chronic stress.

Figure 1

Chronic stress may impair neurons via several mechanisms. Chronic activation of the HPA axis results in hyperactive activation of the axis and increased levels of relevant hormones including corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), circulating glucocorticoids and impairment of dexamethasone feedback (Herman et al., 1995; Mizoguchi et al., 2008; Ulrich-Lai and Herman; 2009). Chronic stress results in an increased neuroinflammatory environment via increases in pro-inflammatory molecules such as interleukin-6 (IL-6), IL-1, tumor necrosis factor alpha (TNFα), and nuclear factor kappa B (NF-κB) and decreases in anti-inflammatory molecules such as IL-10 and transforming growth factor beta (TGFβ) (Grippo et al., 2005; You et al, 2011; Sun et al., 2011). Neurodegeneration increases in the hippocampus after chronic stress at least partly due to increased caspase-3 levels and decreased anti-apoptotic B-cell lymphoma (Bcl-2) levels (Bachis et al., 2008; Kosten et al., 2008; Yang et al., 2011). Dendritic atrophy occurs in several regions including the hippocampus and prefrontal cortex (Magariños and McEwen, 1995a, b; Wellman, 2001; Radley 2004; Cerqueira et al., 2005). Cellular oxidative stress also changes after chronic stress including increases in the superoxide radical O2- and protein and lipid peroxidation (Lucca et al., 2009a, b; Ahmad et al., 2010; Tagliari et al., 2010). Loss of trophic support through decreases in brain-derived neurotrophic factor (BDNF) occurs in the hippocampus and prefrontal cortex after chronic stress (Smith et al., 1995; Song et al., 2006; Adzic et al., 2009). Lastly, chronic stress decreases neurogenesis in the hippocampus as indicated by the loss of bromodeoxyuridine (BrdU) positive cells (Gould and Tanapat, 1999; Pham et al., 2003). Together, these stress-induced cellular and molecular alterations create a harmful neuronal environment that could result in the presentation of depressive and other neuropsychiatric symptoms.