Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations

Abstract

It is well established that when most types of cells, including neurons, are exposed to a mild stress they increase their ability to resist more severe stress. This "preconditioning" phenomenon involves up-regulation of genes that encode cytoprotective proteins such as heat-shock proteins and growth factors. We found that a similar beneficial cellular stress response can be induced in neurons throughout the brain by a "meal-skipping" dietary restriction (DR) regimen in rats and mice. DR is effective in protecting neurons and improving functional outcome in models of stroke, Alzheimer's, Parkinson's and Huntington's diseases. DR induces an increase in the levels of brain-derived neurotrophic factor (BDNF) and heatshock proteins in neurons. DR also stimulates neurogenesis in the hippocampus, and BDNF plays a role in this effect of DR. Physical exercise and environmental enrichment are two other manipulations that have been shown to induce BDNF expression in the brain, presumably because it is a mild cellular stress. When taken together with epidemiological and clinical studies in humans, the data from animal studies suggest that it may be possible to reduce the risk for age-related neurodegenerative disorders through dietary and behavioral modifications that act by promoting neuronal plasticity and survival.

A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila

“…Chronic hypoxia decreased the life span of male Drosophila and this effect can be partially reversed by restriction of dietary amino acids. Recent evidence suggests that DR improves risk factors profiles for protection against cardiovascular diseases in humans [4] and has both cardioprotective and neuroprotective actions in rodent models of ischemic diseases [27], [28]. The identification of dietary amino acids and nutrient signalling as major factors that determines hypoxic survival in the Drosophila model suggest novel possibilities to develop DR mimics and to reduce hypoxic cell death and its consequences in humans.…”

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model

“…These observations are in line with others that already described that EE increases neurogenesis and prevents hippocampal apoptosis (for review, see Hirase andShinohara, 2014 andSale et al, 2014) and it can be related to the improved performance of animals from the EE groups. Although the assessment of the underlying mechanisms of the protective effect of EE is not the aim of the present work, several studies from the literature have pointed to the brain-derived neurotrophic factor (BDNF) as a protective mechanism of EE (Gobbo and O'Mara, 2004;Mattson et al, 2004;Nithianantharajah and Hannan, 2006;Parks et al, 2008;Zhu et al, 2006). Possible mechanisms associated to the beneficial effect of EE, including BDNF, are currently under investigation by our group.…”

Circadian Rhythms, Aging, and Life Span in Mammals

“…The IF-induced beneficial effects are thought to occur independently of the overall caloric intake, but the underlying mechanisms are still unknown. One suggested mechanism is stimulation of cellular stress pathways induced by the IF regimen (7, 116,117). Interestingly, under an IF protocol, when food was introduced during the light period, mice exhibited almost arrhythmicity in clock gene expression in the liver.…”