Abbreviations used : Aβ, amyloid β-peptide ; DHR, dihydrorhodamine ; DR, dietary restriction ; GRP, glucose-regulated protein ; HSP, heat-shock protein ; 3-NP, 3-nitropropionic acid.
Beneficial Effects of Dietary Restriction on Cerebral Cortical Synaptic Terminals
Preservation of Glucose and Glutamate Transport and Mitochondrial Function After Exposure to Amyloid β-Peptide, Iron, and 3-Nitropropionic Acid
Article first published online: 25 DEC 2001
Journal of Neurochemistry
Volume 75, Issue 1, pages 314–320, July 2000
How to Cite
Guo, Z., Ersoz, A., Butterfield, D. A. and Mattson, M. P. (2000), Beneficial Effects of Dietary Restriction on Cerebral Cortical Synaptic Terminals. Journal of Neurochemistry, 75: 314–320. doi: 10.1046/j.1471-4159.2000.0750314.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Alzheimer's disease;
- Cerebral cortex;
- Glucose-regulated protein;
- Heat-shock protein;
- Huntington's disease;
Abstract : Recent studies have shown that rats and mice maintained on a dietary restriction (DR) regimen exhibit increased resistance of neurons to excitotoxic, oxidative, and metabolic insults in experimental models of Alzheimer's, Parkinson's, and Huntington's diseases and stroke. Because synaptic terminals are sites where the neurodegenerative process may begin in such neurodegenerative disorders, we determined the effects of DR on synaptic homeostasis and vulnerability to oxidative and metabolic insults. Basal levels of glucose uptake were similar in cerebral cortical synaptosomes from rats maintained on DR for 3 months compared with synaptosomes from rats fed ad libitum. Exposure of synaptosomes to oxidative insults (amyloid β-peptide and Fe2+) and a metabolic insult (the mitochondrial toxin 3-nitropropionic acid) resulted in decreased levels of glucose uptake. Impairment of glucose uptake following oxidative and metabolic insults was significantly attenuated in synaptosomes from rats maintained on DR. DR was also effective in protecting synaptosomes against oxidative and metabolic impairment of glutamate uptake. Loss of mitochondrial function caused by oxidative and metabolic insults, as indicated by increased levels of reactive oxygen species and decreased transmembrane potential, was significantly attenuated in synaptosomes from rats maintained on DR. Levels of the stress proteins HSP-70 and GRP-78 were increased in synaptosomes from DR rats, consistent with previous data suggesting that the neuroprotective mechanism of DR involves a “preconditioning” effect. Collectively, our data provide the first evidence that DR can alter synaptic homeostasis in a manner that enhances the ability of synapses to withstand adversity.