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

Abstract

Summary: 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.

Caloric restriction improves memory in elderly humans

“…2). In the last 3 decades, numerous studies suggested that modifiable lifestyle factors including a low-calorie diet (caloric restriction, CR), and specific micro-and macronutrients like unsaturated fatty acids (UFA), might exert beneficial effects on the aging brain (3)(4)(5)(6)(7). In animal models of aging and neurodegenerative diseases, CR protected hippocampal, striatal, and cortical neurons, and ameliorated functional decline (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Adaptation and Sensitization to Proteotoxic Stress

“…Only a small number of studies have considered the possibility of preconditioning in models of neurodegenerative diseases and some of these will be described here. First, Mark Mattson has proposed that dietary and behavioral manipulations such as exercise and food restriction may protect against models of neurodegeneration by activating stress-responsive pathways (Duan and Mattson 1999;Guo et al 2000;Mattson et al 2004;Son et al 2008). For example, dietary restriction increases levels of brain derived neurotrophic factor, neurogenesis, and heat shock proteins (Mattson et al 2004).…”

Oral phycocyanobilin may diminish the pathogenicity of activated brain microglia in neurodegenerative disorders

“…It is likely that the most effective neuroprotective regimens will entail the concurrent use of several nutraceuticals and/or drugs that address complementary aspects of the neurodegenerative process 15;96;97 -preferably in conjunction with prudent lifestyle measures. 98 Thus, measures which boost the antioxidant defenses or bioenergetic capacity of neurons, which provide protection from excitotoxicity, which lessen production of amyloid beta, which increase brain production of protective neurotrophic factors, or which work in complementary ways to dampen microglial activation, could be expected to amplify the protection afforded by PCB.…”