Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms

Abstract

Although all cells in the body require energy to survive and function properly, excessive calorie intake over long time periods can compromise cell function and promote disorders such as cardiovascular disease, type-2 diabetes and cancers. Accordingly, dietary restriction (DR; either caloric restriction or intermittent fasting, with maintained vitamin and mineral intake) can extend lifespan and can increase disease resistance. Recent studies have shown that DR can have profound effects on brain function and vulnerability to injury and disease. DR can protect neurons against degeneration in animal models of Alzheimer's, Parkinson's and Huntington's diseases and stroke. Moreover, DR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which may increase the ability of the brain to resist aging and restore function following injury. Interestingly, increasing the time interval between meals can have beneficial effects on the brain and overall health of mice that are independent of cummulative calorie intake. The beneficial effects of DR, particularly those of intermittent fasting, appear to be the result of a cellular stress response that stimulates the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins. Some beneficial effects of DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-D-glucose, which may act as a calorie restriction mimetic. The profound influences of the quantity and timing of food intake on neuronal function and vulnerability to disease have revealed novel molecular and cellular mechanisms whereby diet affects the nervous system, and are leading to novel preventative and therapeutic approaches for neurodegenerative disorders.

Relationships between plasma leptin concentrations and human brain structure: A voxel-based morphometric study

“…In addition, previous studies [32] have shown a positive association between glucocorticoids, whose hyper-secretion is associated with brain atrophy [33], and leptin, thus indicating that the negative correlation between plasma leptin and GM volumes might be somehow mediated by cortisol. Finally, the negative correlation between plasma leptin concentrations and GM volumes of some brain areas may just reflect the negative effect that excess food intake, which stimulates leptin production [34], exerts on brain tissue composition [35]. Further studies are needed to address this important issue.…”

Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke

“…Neurotrophic factors, including BDNF, influence neurogenesis, and it is well known that BDNF-mediated pathways are involved in cell survival and plasticity (Lu and Figurov, 1997;Mattson et al, 2003). For this reason, we investigated whether subchronic ALA treatment could trigger BDNF expression on D10.…”

Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

“…BDNF is a member of a neurotrophin superfamily mainly expressed within the brain. BDNF interacts with TrkB receptor tyrosine kinase, playing several important roles such as; promotion of survival, differentiation and maintenance of neurons in peripheral nervous system and central nervous system; influences to axonal growth and connectivity; participation in the local responses to various types of neuronal stress or insults (Manji et al, 2003;Mattson et al, 2003). Furthermore, it also has been reported that the gene encoding BDNF might be an important candidate for susceptibility of neuropsychiatric disorders including bipolar disorder (Neves-Pereira et al, 2002;Sklar et al, 2002;Hashimoto et al, 2004), schizophrenia (Krebs et al, 2000), Parkinson's disease (Momose et al, 2002), and Alzheimer's disease (Ventriglia et al, 2002).…”