Effects of docosahexaenoic acid on age-related changes in the synaptic plasma membrane proteome

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAAA	PROTEOM-3

Authors

• V. K. Sidhu
• H. Y. Kim

Abstract

Despite advances in our understanding of age-related changes in the brain, little is known about the etiology of cognitive impairment with age. We have previously demonstrated that synaptic plasma membrane (SPM) proteins involved in neurotransmission were down-regulated in DHA-deprived brains, suggesting an important role of DHA in supporting synaptic function. In this study, we investigated the role of DHA in age-related regulation of synaptic proteins. We compared SPM proteome from young (4 month old) and aged (15 month old) mice brains using nano-LC-MS/MS after SDS-PAGE, label-free and 16O/18O labeling of tryptic peptides. The differentially expressed proteins were validated by western blot analysis and/or mRNA analysis. We found reduced expression of 17 proteins including Glutamate receptors- NMDA subunit 2 and AMPA2, munc18-1, PSD-95, sv2b, dynamin-1, VAMP2, SNAP25, septin-3, neuroplastin, glutamate transporters- excitatory amino acid transporter1 and vesicular glutamate transporter 1, fodrin-alpha, rab3A, neuroplastin, SNAP-alpha and synaptopodin. A positive effect of DHA was observed for PSD-95, synaptopodin, sv2b, SNAP-alpha, NR2b, AMPA2 receptor and fodrin-alpha. Under DHA deprived conditions, these proteins were further down-regulated with aging while DHA-adequate diet restored the levels significantly indicating that DHA plays an important role in maintaining the status of some of the synaptic proteins during aging.

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