Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome
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- 作者：Vishaldeep K. Sidhu ; Bill X. Huang ; Abhishek Desai ; Karl Kevala ; Hee-Yong Kim ; hykim@nih.gov" class="auth_mail" title="E-mail the corresponding author
- 关键词：Aging-related changes ; Synaptic plasma membrane proteins ; DHA ; Neurotransmission ; MS&ndash ; based protein quantitation ; Mass spectrometry ; Recognition memory
- 刊名：Neurobiology of Aging
- 出版年：2016
- 出版时间：May 2016
- 年：2016
- 卷：41
- 期：Complete
- 页码：73-85
- 全文大小：1921 K
文摘
Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)–deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry–based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function.