The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically?

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• 作者：Cai Song^a ; ^b ; ^c ; ^{cai.song@dal.ca" class="auth_mail" title="E-mail the corresponding author} ; Chu-Hsin Shieh^b ; Yi-Shyuan Wu^b ; Allan Kalueff^a ; ^d ; ^e ; Siddharth Gaikwad^b ; Kuan-Pin Su^b
• 关键词：Aβ ; amyloid β ; AA ; arachidonic acid ; AD ; Alzheimer's disease ; ALA ; α-linolenic acid ; APP ; amyloid precursor proteins ; BDNF ; brain-derived neurotrophic factor ; CNS ; central nervous system ; CSF ; cerebral spinal fluid ; COX2 ; cyclooxygenase 2 ; DHA ; docosahexaenoic acid ; DPA ; docosapentaenoic acid ; EC ; entorhinal cortex ; ER ; endoplasmic reticulum ; EPA ; eicosapentaenoic acid ; GC-SF ; granulocyte colony-stimulating factor ; HPA ; hypothalamic&ndash ; pituitary adrenal ; IL ; interleukin ; JNK ; Jun-N-terminal k
• 刊名：Progress in Lipid Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：62
• 期：Complete
• 页码：41-54
• 全文大小：827 K

文摘

Omega-3 polyunsaturated fatty acids (n‐3-PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve or prevent some psychiatric and neurodegenerative diseases in both experimental and clinical studies. As important membrane components, these PUFAs benefit brain health by modulating neuroimmune and apoptotic pathways, changing membrane function and/or competing with n‐6 PUFAs, the precursors of inflammatory mediators. However, the exact role of each fatty acid in neuroimmune modulation and neurogenesis, the interaction between EPA and DHA, and the best EPA:DHA ratios for improving brain disorders, remain unclear. It is also unknown whether EPA, as a DHA precursor, acts directly or via DHA. Here, we discuss recent evidence of EPA and DHA effects in the treatment of major depression and Alzheimer's disease, as well as their potential synergistic action on anti-inflammatory, antioxidant and neurotrophic processes in the brain. We further analyze the cellular and molecular mechanisms by which EPA, DHA or their combination may benefit these diseases. We also outline the limitations of current studies and suggest new genetic models and novel approaches to overcome these limitations. Finally, we summarize future strategies for translational research in this field.