Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome

Decreased cognitive performance reduces independence and quality of life for aging individuals. Healthy brain aging does not involve significant neuronal loss, but little is known about the effects of aging at synaptic terminals. Age-related cognitive decline likely reflects the manifestation of dysregulated synaptic function and ineffective neurotransmission. In this study, hippocampal synaptosomes were enriched from young-adult (3 months), adult (12 months), and aged (26 months) Fischer 344 x Brown Norway rats, and quantitative alterations in the synaptoproteome were examined by 2-DIGE and MS/MS. Bioinformatic analysis of differentially expressed proteins identified a significant effect of aging on a network of neurotransmission-regulating proteins. Specifically, altered expression of DNM1, HPCA, PSD95, SNAP25, STX1, SYN1, SYN2, SYP, and VAMP2 was confirmed by immunoblotting. 14-3-3 isoforms identified in the proteomic analysis were also confirmed as a result of their implication in the regulation of the synaptic vesicle cycle and neurotransmission modulation. The findings of this study demonstrate a coordinated down-regulation of neurotransmission-regulating proteins that suggests an age-based deterioration of hippocampal neurotransmission occurring between adulthood and advanced age. Altered synaptic protein expression may decrease stimulus-induced neurotransmission and vesicle replenishment during prolonged or intense stimulation, which are necessary for learning and the formation and perseverance of memory.