Hormesis

Hormesis

UltimaimgHormesis is an adaptive response of cells and organisms to a moderate stress, usually intermittent, which may have many beneficial effects to the biological system. Examples include exposure to low doses of certain phytochemicals such as curcumin, resveratrol and isothiocyanates, exercise and intermittent fasting dietary restriction. The latter, when it does not cause malnutrition, induces a moderate nutritional stress to the organism, which not only stimulates the stress proteins, but also the body’s defense mechanisms, making the cell or the organism more resistant to toxic stimuli. In general, intermittent fasting seems to act by mechanisms associated with cell survival and inflammatory response, thereby involving nuclear transcription factor kappa B (NF-kB) modulation. However, little is known about the molecular mechanisms involved, as well as the involvement of hormesis in signaling pathways important to neurogenesis and neuroprotection, such as the cyclic AMP response element (CREB) and WNT, and its correlation with inflammatory signaling. The present work investigates the effects of intermittent fasting on memory and learning, the signaling mechanisms associated with WNT proteins, CREB and NF-kB transcription factors and gene expression regulated by these transcription factors in rat hippocampus in absence or presence of an inflammatory stimulus, represented by intravenous administration of lipopolysaccharide (LPS). The results showed that intermittent fasting improved performance in Barnes maze and inhibitory avoidance behavioral tests even when treated with LPS. Also, intermittent fasting induced both increase of phosphorylated CREB and canonical WNT signaling pathway, and changes in inflammatory mRNA markers levels, such as, decreasing of toll-like receptor-4 (Tlr-4), induced nitric oxide synthase (iNos) and cyclooxygenase 2 (Cox-2). In addition, intermittent fasting can also increase interleukin (IL)-10/tumor necrosis factor (TNF) ratio levels when compared to control group. Taken together, our results suggest that intermittent fasting dietary restriction induces a prevalence of protective signaling cascades in the central nervous system (CNS).