Brain‐derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice

Abstract

Dietary restriction (DR; reduced calorie intake) increases the lifespan of rodents and increases their resistance to cancer, diabetes and other age-related diseases. DR also exerts beneficial effects on the brain including enhanced learning and memory and increased resistance of neurons to excitotoxic, oxidative and metabolic insults. The mechanisms underlying the effects of DR on neuronal plasticity and survival are unknown. In the present study we show that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex and striatum of mice maintained on an alternate day feeding DR regimen compared to animals fed ad libitum. Damage to hippocampal neurons induced by the excitotoxin kainic acid was significantly reduced in mice maintained on DR, and this neuroprotective effect was attenuated by intraventricular administration of a BDNF-blocking antibody. Our findings show that simply reducing food intake results in increased levels of BDNF in brain cells, and suggest that the resulting activation of BDNF signaling pathways plays a key role in the neuroprotective effect of DR. These results bolster accumulating evidence that DR may be an effective approach for increasing the resistance of the brain to damage and enhancing brain neuronal plasticity.

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

“…When the excitotoxin kainic acid (KA) is injected into the dorsal hippocampus of mice it induces seizures and damage to pyramidal neurons in regions CA3 and CA1 (14). KA was injected into the dorsal hippocampus of mice that had been maintained for 24 weeks on AL, LDF, and IF diets.…”

“…Kainate was injected stereotaxically into the dorsal aspect of the right hippocampus by using the methods described (14). Briefly, mice were anesthetized with Avertin and placed in a stereotaxic head holder, and the skull was exposed along the midline.…”

“…To gain insight into the nature of the underlying mechanism, we compared the effects of LDF and IF diets on several parameters that have been postulated to play a role in the protective effects of DR including body weight, food intake, and fasting levels of serum insulin, glucose, and insulin-like growth factor 1 (IGF-1). In addition, recent studies have shown that rats and mice maintained on an IF regimen exhibit increased resistance of neurons in their brains to insults relevant to the pathogenesis of several different human neurological disorders including epileptic seizures and stroke (6,8,14). We therefore performed an experiment to determine whether LDF and IF diets exert similar beneficial effects on neurons in the brain.…”

Food restriction enhances visual cortex plasticity in adulthood

“…In accordance with this hypothesis, it has been reported that a brief period of FR after spinal chord injury is not associated with cortical or spinal chord enhancement of BDNF 45 . In all works showing an increase in BDNF signalling after FR, either adult animals restricted for 3 months or aged mice maintained under dietary regimen for their whole life were used [46][47][48][49] .…”

Effect of Resveratrol as Caloric Restriction Mimetic and Environmental Enrichment on Neurobehavioural Responses in Young Healthy Mice

“…Both resveratrol and environmental enrichment have also been reported to extend lifespan and improve motor function in drosophila and rat models of Parkinson's disease, respectively, by activating sirtuins gene [15,38]. Caloric restriction and EE have been found to attenuate age-related deficits in learning and memory [15,39] and increase resistance of neurons to excitotoxic, oxidative, and metabolic insults and improve behavioural outcomes in experimental models of Alzheimer's and Huntington's disease [40]. The result obtained from this study using the elevated plus maze for memory, though not statistically significant, showed a slight decrease ( > 0.05) in the transfer latency (retention) across the groups when compared to the control with the least mean value obtained in the EE group.…”