Figure 1 Venn diagrams of differentially expressed proteins (biomarkers) illustrate the common and shared inflammatory factors associated with depressive (A) and neuropsychiatric (B) symptom severities. BDNF Alterations in neurogenesis and neuronal plasticity are cell assay observed in a number of CNS disorders that contain inflammatory processes. BDNF (a member of the neurotrophic factor family) is implicated as a key mediator of this plasticity,
and inflammatory cytokines (e.g., IL-1β) #selleck chemical Bortezomib keyword# can decrease BDNF signaling (Tong et al. 2008; Cortese et al. 2011). Regulation of BDNF expression and function contributes, in part, to the pathophysiology and treatment
of depression (Chen et al. 2001; Sen et al. 2008). Both the Val66Met BDNF Inhibitors,research,lifescience,medical polymorphism (rs6265) and BDNF levels have been associated with depression (Egan et al. 2003; Hashimoto 2010). BDNF levels also correlate with treatment outcomes, and may, therefore, be a useful biomarker for prognosis (Kurita et al. 2012). Importantly, for patients with HCV, BDNF levels appear Inhibitors,research,lifescience,medical to influence resiliency against developing depression during interferon-α-based therapies (Lotrich et al. 2012). IL-23 IL-23 is an important mediator of the inflammatory response against infection. In conjunction with IL-6 and transforming growth factor (TGF)-β 1, IL-23 stimulates naive CD4+ T cells to differentiate into Th17 cells (T-cell subsets that produce IL-17, a proinflammatory cytokine Inhibitors,research,lifescience,medical that can stimulate the production of other proinflammatory factors, such as IL-1, IL-6, and TNF-α; Kikly et al. 2006; Langowski et al. 2006). Although little is known about its role in brain and effect on neuropsychiatric function, inhibition of the IL-12/IL-23 pathway reduces microglia activation Inhibitors,research,lifescience,medical and improves
cognitive function and related pathology in an Alzheimer’s disease mouse model (Vom Berg et al. 2012). Similarly, knockout mice deficient in either IL-23 subunits p40 or p19, or in either subunit of the IL-23 receptor (IL-23R and IL12R-β1) develop less severe symptoms of multiple sclerosis and inflammatory bowel disease (Gran et al. Batimastat 2004; Yen et al. 2006). Consistent with these observations, we found that increased plasma IL-23 concentrations were associated with increased depression severity ratings (Table 4; Fig. 1); however, more research is needed to investigate the role of IL-23 signaling in CNS inflammatory diseases, including depression. RANTES Regulated upon Activation, Normal T-cell Expressed, and Secreted (a.k.a.