Instead, normal age-related changes in gene function may represen

Instead, normal age-related changes in gene function may represent latent vulnerability Ibrutinib factors that are promoted by aging, and that may directly contribute in the disease process (ie, causing or associated with disease) in the context of additional genetic and/or environmental

risk factors, which exacerbate age-dependent trajectories. Conversely, moderating factors that delay age-dependent trajectories may promote resiliency not only against age-related Inhibitors,research,lifescience,medical declines but also against multiple brainrelated disorders. Molecular interaction between depression and aging: the cases of BDNF, SST, and dendritic inhibition An example of a putative interaction between age and disease is provided by the investigation of BDNF and BDNF-dependent genes. BDNF is a signaling neuropeptide that is critical during development Inhibitors,research,lifescience,medical and adulthood, specifically in maintaining plasticity and proper functioning of many targeted neuronal cells. Reduced BDNF levels and/or

functions have been implicated in multiple brain-related disorders, including major depression,10,13,14 bipolar depression, schizophrenia, Huntington’s disease, and Alzheimer’s disease,9-16 Interestingly, Inhibitors,research,lifescience,medical BDNF is also downregulated with increasing age. A normal non-psychiatric control subject may lose as much as 60% of BDNF expression between the ages of 20 and 60 years.7,17 We have reported evidence of decreased BDNF levels and/or signaling in the amygdala and anterior cingulate cortex of subjects affected with depression compared

to controls.10,14,62 We have also reported reduced expression of SST, cortistatin (CORT), and neuropeptide Y (NPY) in the same cohorts. SST, CORT, and NPY are neuropeptides that Inhibitors,research,lifescience,medical are expressed in subtypes of γ-aminobutyric acid (GABA) interneurons, which specifically target Inhibitors,research,lifescience,medical the dendrites of pyramidal neurons (Figure 3a). SST, CORT, and NPY expressions are dependent on BDNF signaling, as demonstrated by reduced levels in mice with genetically-induced reduction in BDNF functions.14,62,-63 Together, these findings have Endonuclease suggested the presence of a depression-related pathogenic mechanism linking reduced BDNF function to reduced markers of GABA interneurons that provide dendritic inhibition. Figure 3. Dendritic inhibition, a biological module at the intersection of age and psychiatric disorders. A) Excitatory pyramidal neurons (PYR) are regulated by different types of inhibitory γ-aminobutyric acid (GABA) neurons. Somatostatin (SST)-, neuropeptide … Given that not all elderly subjects develop depression, additional factors must be at play. Indeed, the cross-sectional slope of decrease in BDNF expression in subjects with depression appears to parallel that of control subjects, but at a lower level, demonstrating reduced expression at most ages (Figure 3b).

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