Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat

Brain aging is related to the numerous structural and functional changes including decreased synaptic plasticity. The beneficial effects of dietary restriction (DR) are well known but insufficiently investigated at the level of plasticity-related markers. Therefore, the aim of this study was to examine the expression profiles of proteins structurally and functionally related to synapses—growth-associated protein 43 (GAP-43), synaptophysin (SPH) and α-synuclein (α-Syn), in the course of aging and in response to long-term DR.The mRNA and protein levels of three presynaptic proteins were assessed by Real Time RT-PCR and Western blotting in the cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old (24-month-old) male Wistar rats fed ad libitum and exposed to DR starting from 6 months of age. We observed that long-term DR modulated age-related transcriptional changes by maintaining stable mRNAs levels in the cortex. No major age-related changes of the protein levels were observed in the cortex, while the specific temporal decline was detected in the hippocampus for all three proteins. The SPH levels were decreased across lifespan (0.8-, 0.8- and 0.6-fold change at 12, 18 and 24 months), while the significant decrease of GAP-43 and α-Syn protein was detected at 24 months of age (0.6- and 0.7-fold decrease, respectively). Long-term DR eliminated this decline by increasing GAP-43, SPH and α-Syn protein levels (1.7-, 1.7- and 1.6-fold, respectively) thus reverting protein levels to the values measured in 6-month-old animals.Specific pattern of changes observed in the hippocampus identifies this structure as more vulnerable to the processes of aging and with a more pronounced response to the DR effects. The observed DR-induced stabilization of the levels of three presynaptic proteins indicates the beneficial effect of DR on age-related decline in the capacity for synaptic plasticity.